# One-year real-life targeted next generation sequencing for lymphoma diagnosis: study of patients from the French Lymphoma Network in Rhône-Alpes

C Bommier, C Mauduit, J Fontaine, E Bourbon, Pierre Sujobert, Sarah Huet, Lucile Baseggio, S Hayette, Camille Laurent, Emmanuel Bachy, et al.

<figure><img src="image_1.png" /></figure>

## ► To cite this version:

C Bommier, C Mauduit, J Fontaine, E Bourbon, Pierre Sujobert, et al.. One-year real-life targeted next generation sequencing for lymphoma diagnosis: study of patients from the French Lymphoma Network in Rhône-Alpes. 15th International Conference on Malignant Lymphoma, Jun 2019, Lugano, Switzerland., Hematological Oncology, 136, pp.186, 10.1002/hon.2630. inserm-04831184

HAL Id: inserm-04831184

https://inserm.hal.science/inserm-04831184v1

Submitted on 11 Dec 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

Public Domain
Hematological Oncology

15th International Conference on Malignant Lymphoma
Palazzo dei Congressi, Lugano, Switzerland
18-22 June, 2019
# Hematological ONCOLOGY

## Editor-in-Chief

Francesco Bertoni

Lymphoma & Genomics Research Program, IOR Institute of Oncology Research Lymphoma Unit, IOSI Oncology Institute of Southern Switzerland via Vela 6, 6500 Bellinzona, Switzerland
Email: frbertoni@me.com

## Associate Editors

Andrés J.M. Ferreri
Milan, Italy

Ayalew Tefferi
Rochester, USA

Gerald Niedobitek
Berlin, Germany

## Editorial Board

J.O. Armitage
Omaha, USA

G. Bhagat
New York, USA

M. Bronchud
Barcelona, Spain

F Cabanillas
Houston, USA

A.M. Carella
Genova, Italy

M. Dreyling
Munich, Germany

P.A. Hall
Belfast, UK

H.C. Hasselbalch
Odense, Denmark

D.K. Hossfeld
Hamburg, Germany

P. Johnson
Southampton, UK

A.M. Levine
Los Angeles, USA

R. Liang
Hong Kong, China

S. Nakamura
Nagoya, Japan

G.A. Pangalis
Athens, Greece

M. Ponzoni
Milan, Italy

D. Rossi
Bellinzona, Switzerland

U. Tirelli
Aviano, Italy

K. Tobinai
Chuo-ku, Japan

M. Trneny
Prague, Czech Republic

R.W. Tsang
Toronto, Canada

J. Westermann
Berlin, Germany

E. Zucca
Bellinzona, Switzerland

## Aims and Scope

Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:

* Clinical practice and management of hematological neoplasia, including

- Acute and chronic leukemias

- Malignant lymphomas

- Myeloproliferative disorders

* Diagnostic investigations, including imaging and laboratory assays

* Epidemiology, pathology and pathobiology of hematological neoplasia

* Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies

* Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoiesis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.

Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance. The Journal may be viewed and manuscripts submitted online at http://wileyonlinelibrary.com/journal/hon

## Copyright

Copyright © 2019 John Wiley & Sons, Ltd. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means without the prior permission in writing from the copyright holder. Authorization to photocopy items for internal and personal use is granted by the copyright holder for libraries and other users registered with their local Reproduction Rights Organisation (RRO), e.g. Copyright Clearance Center (CCC), 222 Rosewood Drive, Danvers, MA 01923, USA (www.copyright.com), provided the appropriate fee is paid directly to the RRO. This consent does not extend to other kinds of copying such as copying for general distribution, for advertising or promotional purposes, for creating new collective works or for resale. Special requests should be addressed to: permissionsuk@wiley.com

## Disclaimer

The Publisher and Editors cannot be held responsible for errors or any consequences arising from the use of information contained in this journal; the views and opinions expressed do not necessarily reflect those of the Publisher, Society and Editors, neither does the publication of advertisements constitute any endorsement by the Publisher and Editors of the products advertised.
Contents

5 Acknowledgements

10 Scientific Program

27 Satellite Symposium Program and Agenda

34 Oral Presentations

186 Poster Presentations

339 Publications

554 Ongoing Trials

575 Author Index

606 Keyword Index
15th International Conference on Malignant Lymphoma
Palazzo dei Congressi, Lugano (Switzerland)
18 - 22 June, 2019

Organized by the Foundation for the Institute of Oncology Research (IOR) in cooperation with the American Association for Cancer Research (AACR)

15-ICML has been accredited by the European Accreditation Council for Continuing Medical Education (EACCME®) for a maximum of 30 European CME credits (ECMEC®s).

Each medical specialist should claim only those credits that he/she actually spent in the educational activity.

The EACCME® is an institution of the European Union of Medical Specialists (UEMS), www.uems.eu.

Through an agreement between the European Union of Medical Specialists and the American Medical Association, physicians may convert EACCME® credits to an equivalent number of AMA PRA Category 1 Credits™. Information on the process to convert EACCME® credits to AMA credits can be found at www.ama-assn.org/education/earn-credit-participation-international-activities.

Live educational activities occurring outside of Canada, recognised by the UEMS-EACCME® for ECMEC® credits are deemed to be Accredited Group Learning Activities (Section 1) as defined by the Maintenance of Certification Program of the Royal College of Physicians and Surgeons of Canada.

The meeting is accredited with 25 ESMO-MORA cat.1 points.

Disclaimer: This Abstract Book has been produced using author-supplied copy. Editing has been restricted to some corrections of spelling and style where appropriate. No responsibility is assumed for any claims, instructions, methods or drug dosages contained in the abstracts: it is recommended that these are verified independently.
ACKNOWLEDGEMENTS

INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA (ICML) and FOUNDATION FOR THE
INSTITUTE OF ONCOLOGY RESEARCH (IOR) PRESIDENT

Franco Cavalli, Bellinzona (Switzerland)

ORGANIZING COMMITTEE CHAIRMAN

Michele Ghielmini, Bellinzona (Switzerland)

ORGANIZING COMMITTEE

(based in Bellinzona, Switzerland)

Francesco Bertoni

Alden A. Moccia

Bertrand Nadel, Marseilles (France) - American Association for Cancer Research (AACR) representative

Fedro A. Peccatori, Milan (Italy) - European School of Oncology (ESO) representative

Davide Rossi

Anastasios Stathis

Georg Stüssi

Emanuele Zucca

ADVISORY BOARD

James O. Armitage, Omaha, NE (USA) - CHAIRMAN

Elias Campo, Barcelona (Spain)

Bruce D. Cheson, Washington, D.C. (USA)

Nicholas Chiorazzi, Manhasset, NY (USA)

Wee Joo Chng, Singapore (Singapore)

Riccardo Dalla-Favera, New York, NY (USA)

Stephan Dirnhofer, Basel (Switzerland)

Martin Dreyling, Munich (Germany)

Andreas Engert, Cologne (Germany)

Jonathan W. Friedberg, Rochester, NY (USA)

Gianluca Gaidano, Novara (Italy)

Philippe Gaulard, Créteil (France)

Mary K. Gospodarowicz, Toronto, ON (Canada)

Peter W.M. Johnson, Southampton (UK)

Brad S. Kahl, St. Louis, MO (USA)

Ralf Küppers, Essen (Germany)

John P. Leonard, New York, NY (USA)

T. Andrew Lister, London (UK)

Markus G. Manz, Zurich (Switzerland)

Ari M. Melnick, New York, NY (USA)

Koichi Ohshima, Kurume (Japan)

Astrid Pavlovsky, Buenos Aires (Argentina)

Leticia Quintanilla-Martinez de Fend, Tübingen (Germany)

S.Vincent Rajkumar, Rochester, MN (USA)

Kerry J. Savage, Vancouver BC (Canada)

John F. Seymour, Melbourne (Australia)

Margaret A. Shipp, Boston, MA (USA)

Lena Specht, Copenhagen (Denmark)

Catherine Thieblemont, Paris (France)

Umberto Vitolo, Turin (Italy)
Anas Younes, New York, NY (USA)

Wilhelm Wössmann, Hamburg (Germany)

Weili Zhao, Shangai (China)

## CONFERENCE SECRETARIAT AND LOCAL ORGANISATION

Cristiana Brentan, Orietta Lugli, Chiara Saporiti

Bellinzona (Switzerland)

## THE CONFERENCE ORGANISERS WISH TO THANK THE FOLLOWING SPONSORS FOR THEIR UNRESTRICTED FINANCIAL SUPPORT:

(updated on May 15, 2019)

AbbVie

Acerta Pharma, a member of the Astra Zeneca group

Affimed

Atara Biotherapeutics Switzerland GmbH

Bayer

Bristol-Myers Squibb

Celgene Corporation

Celltrion Healthcare

Gilead Sciences

HTG Molecular Diagnostics

Incyte Corporation

IQone, a Clinigen company

Janssen Pharmaceutical Companies of Johnson & Johnson

Karyopharm Therapeutics

Kite, a Gilead Company

Lymphoma Hub

Loxo Oncology

MorphoSys

MSD

Mundipharma International Limited

Nordic Nanovector

Novartis Oncology

Pfizer Oncology

Roche

Sandoz

Seattle Genetics

Stemline Therapeutics

Takeda Oncology

## THE CONFERENCE ORGANISERS WISH TO THANK THE FOLLOWING CONTRIBUTORS FOR THEIR SUPPORT:

(updated on May 15, 2019)

American Association for Cancer Research - AACR

City of Lugano

European Canine Lymphoma Network

European School of Multimodality Imaging & Therapy - ESMIT

European School of Oncology - ESO

European Society for Medical Oncology - ESMO

IBSA Foundation for Scientific Research
International Extranodal Lymphoma Study Group - IELSG

International Lymphoma Radiation Oncology Group - ILROG

Kompetenznetz Maligne Lymphome e.V. - KML

Leukemia & Lymphoma Society - LLS

Lymphome.ch Patientennetz Schweiz

San Salvatore Foundation

Saudi Society of Blood & Marrow Transplantation - SS-BMT

Swiss Cancer League

Swiss Cancer Research Foundation

Ticino Tourism

Union for China Lymphoma Investigators - UCLI

Università della Svizzera Italiana - USI

## 15-ICML REVIEWERS' LIST

THE 15-ICML ORGANIZING COMMITTEE WISHES TO THANK THE FOLLOWING COLLEAGUES AND FRIENDS FOR THEIR PROFESSIONAL HELP:

R.H. Advani, Stanford, CA (USA)

S. Ansell, Rochester, MN (USA)

T.T. Batchelor, Boston, MA (USA)

P. Boffetta, New York, NY (USA)

C. Buske, Ulm (Germany)

E. Campo, Barcelona (Spain)

L. Ceriani, Bellinzona (Switzerland)

B. Chapuy, Göttingen (Germany)

B.D. Cheson, Washington, D.C. (USA)

N. Chiorazzi, Manhasset, NY (USA)

R. Dalla-Favera, New York, NY (USA)

A. Davies, Southampton (UK)

L. de Leval, Lausanne (Switzerland)

S. Dirnhofer, Basel (Switzerland)

R. Dolcetti, Aviano (Italy)

M. Dreyling, Munich (Germany)

K. Dunleavy, Bethesda, MD (USA)

A. Engert, Cologne (Germany)

M. Federico, Modena (Italy)

A.J. Ferreri, Milan (Italy)

F. Forconi, Southampton (UK)

J.W. Friedberg, Rochester, NY (USA)

P. Gaulard, Créteil (France)

B. Gerber, Bellinzona (Switzerland)

M.K. Gospodarowicz, Toronto (Canada)

M. Hallek, Cologne (Germany)

G. Illerhaus, Stuttgart, Germany

P.W.M. Johnson, Southampton (UK)

B.S. Kahl, St. Louis, MO (USA)

R. Küppers, Essen (Germany)

G. Lenz, Muenster (Germany)

J.P. Leonard, New York, NY (USA)

A. Lopez-Guillermo, Barcelona (Spain)

I.S. Lossos, Miami, FL (USA)

S. Luminari, Reggio Emilia (Italy)
D.G. Maloney, Seattle, WA (USA)

M.G. Manz, Zurich (Switzerland)

M.V. Mateos, Salamanca (Spain)

M. Meignan, Créteil (France)

A.M. Melnick, New York, NY (USA)

S. Montoto, London (UK)

B. Nadel, Marseille (France)

G.S. Nowakowski, Rochester, MN (USA)

S.M. O'Brien, Irvine, CA (USA)

O.A. O'Connor, New York, NY (USA)

K. Ohshima, Kurume (Japan)

L. Pasqualucci, New York, NY (USA)

P. Martin, New York, NY (USA)

L. Quintanilla-Martinez de Fend, Tübingen (Germany)

M. Raderer, Vienna (Austria)

J. Radford, Manchester (UK)

S.V. Rajkumar, Rochester, MN (USA)

U. Ricardi, Turin (Italy)

S. Rule, Plymouth (UK)

G. Salles, Lyon (France)

K.J. Savage, Vancouver, B.C. (Canada)

M. Seto, Nagoya (Japan)

M.A. Shipp, Boston, MA (USA)

S.M. Smith, Chicago, IL (USA)

L. Specht, Copenhagen (Denmark)

M. Spina, Aviano (Italy)

M. Trněný, Prague (Czech Republic)

U. Vitolo, Turin (Italy)

J.M. Vose, Omaha, NE (USA)

W. Wössmann, Hamburg (Germany)

A. Younes, New York, NY (USA)

W. Zhao, Shanghai (China)

P.L. Zinzani, Bologna (Italy)

SAVE THE DATE: 16-th International Conference on Malignant Lymphoma
Lugano, Switzerland
June 15-19, 2021
# 15-ICML - 15th INTERNATIONAL CONFERENCE ON
MALIGNANT LYMPHOMA

Lugano, Switzerland-June 18-22, 2019

www.lymphcon.ch

SCIENTIFIC PROGRAM (as of May 15, 2019)

## Tuesday, June 18, 2019

08:30-17:10
Auditorium
(USI Università)

CLOSED WORKSHOP - BRIDGING LIQUID BIOPSY INTO MANAGEMENT OF LYMPHOMA PATIENTS: DEVELOPMENT OF FRAMEWORKS FOR CLINICAL RESEARCH AND RECOMMENDATIONS FOR CLINICAL PRACTICE

Co-chairs: D. Rossi, Bellinzona (Switzerland), W.H. Wilson, Bethesda, MD (USA) and E. Zucca, Bellinzona (Switzerland)

Organized in co-operation with the American Association for Cancer Research-AACR and the European School of Oncology-ESO

and with the endorsement of the Leukemia & Lymphoma Society - LLS
by invitation only

15:00-17:15
Aula Magna
(USI Università)

WORKSHOP-NEW GUIDELINES FROM THE INTERNATIONAL LYMPHOMA RADIATION ONCOLOGY GROUP - ILROG

Organized in collaboration with the International Lymphoma Radiation Oncology Group - ILROG
open to all 15-ICML attendees

### PART 1-NEW GUIDELINES FROM ILROG

Chair: L. Specht, Copenhagen (Denmark)

15:00

RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA
A. Ng, Boston, MA (USA)

15:15

SOLITARY PLASMACYTOMA AND MULTIPLE MYELOMA
R. Tsang, Toronto (Canada)

15:30

IMAGING IN RADIATION THERAPY FOR LYMPHOMA
G. Mikhaeel, London (UK)

15:45

PROTON THERAPY FOR MEDIASTINAL LYMPHOMAS
B.S. Dabaja, Houston, TX (USA)

16:00

DISCUSSION

16:15

COFFEE BREAK inside Aula Magna (USI Università), for attendees

### PART 2 - PANEL DISCUSSION

Led by J. Plastaras, Philadelphia, PA (USA)

16:30

FUTURE GUIDELINES TO BE DEVELOPED; ISSUES TO BE CONSIDERED IN ILROG GUIDELINES

16:50

HOW TO DISSEMINATE AND USE ILROG GUIDELINES

## Wednesday, June 19, 2019

08:30-09:15

Article Nr

"MEET THE PROFESSOR" SESSIONS

5 parallel sessions

Room A

EB09

MULTIPLE MYELOMA: EVERY YEAR A NEW STANDARD?
S.V. Rajkumar, Rochester, MN (USA)
repeated on Thursday, June 20, in Room B

(Continues)
<table><tbody><tr><td>Room B</td><td>EB10</td><td>THE MODERN APPROACH TO MANTLE CELL LYMPHOMA<br>S. Rule, Plymouth (UK)<br>repeated on Thursday, June 20, in Room A</td></tr><tr><td>Cinema Corso</td><td>EB07</td><td>MANAGING THE TOXICITIES OF CAR T-CELL THERAPY<br>S.S. Neelapu, Houston, TX (USA)<br>repeated on Friday, June 21, in Auditorium (USI Università)</td></tr><tr><td>Auditorium<br>(USI Università)</td><td>EB01</td><td>PCNSL, A CURABLE DISEASE<br>T.T. Batchelor, Boston, MA (USA)<br>repeated on Thursday, June 20, in Cinema Corso</td></tr><tr><td>Aula Magna<br>(USI Università)</td><td>EB12</td><td>WHAT WE SHOULD KNOW ABOUT NK/T-CELL LYMPHOMAS<br>W. Zhao, Shanghai (China)<br>offered only once</td></tr><tr><td>09:00-12:00<br>Marquee</td><td colspan="2">POSTER SESSION SET UP</td></tr><tr><td>09:30-10:15</td><td colspan="2">5 parallel sessions</td></tr><tr><td>Room A</td><td>EB02</td><td>DOUBLE HIT LYMPHOMA, SO WHAT?<br>A. Davies, Southampton (UK)<br>repeated on Friday, June 21, in Room B</td></tr><tr><td>Room B</td><td>EB05</td><td>HOW TO APPROACH CLL IN CLINICAL PRACTICE<br>M. Hallek, Cologne (Germany)<br>repeated on Friday, June 21, in Room A</td></tr><tr><td>Cinema Corso</td><td>EB11</td><td>LIQUID BIOPSY IN NON-HODGKIN'S LYMPHOMA<br>W.H. Wilson, Bethesda, MD (USA)<br>repeated on Thursday, June 20, in Auditorium (USI Università)</td></tr><tr><td>Auditorium<br>(USI Università)</td><td>EB06</td><td>CUTANEOUS LYMPHOMAS<br>W. Kempf, Zurich (Switzerland)<br>repeated on Friday, June 21, in Cinema Corso</td></tr><tr><td>Aula Magna<br>(USI Università)</td><td>EB03</td><td>BREAST IMPLANT ASSOCIATED ALCL AND OTHER RARE T-CELL LYMPHOMAS<br>L. de Leval, Lausanne (Switzerland)<br>offered only once</td></tr><tr><td>10:15-10:35<br>Marquee, Cinema Corso<br>and USI Università</td><td colspan="2">COFFEE BREAK</td></tr><tr><td>10:35-12:00</td><td colspan="2">EDUCATIONAL SYMPOSIA 📉<br>2 parallel sessions</td></tr><tr><td>Room A, Cinema Corso,<br>Auditorium and Aula Magna<br>(USI Università)</td><td colspan="2">TREATING HODGKIN LYMPHOMA IN THE NEW MILLENNIUM<br>Chair: A. Engert, Cologne (Germany)</td></tr><tr><td>EB13</td><td colspan="2">OPTIONS FOR FIRST LINE THERAPY OF HODGKIN LYMPHOMA<br>P.W.M. Johnson, Southampton (UK)</td></tr><tr><td>EB14</td><td colspan="2">RELAPSED AND REFRACTORY DISEASE<br>A.S. LaCasce, Boston, MA (USA)</td></tr><tr><td>EB15</td><td colspan="2">TREATMENT OF ELDERLY HODGKIN LYMPHOMA PATIENTS<br>A. Engert, Cologne (Germany)</td></tr><tr><td>Room B<br>and Marquee</td><td colspan="2">NEW DRUGS FOR NON-HODGKIN LYMPHOMA: BEYOND CHEMOTHERAPY<br>Chair: G. Salles, Lyon (France)</td></tr><tr><td>EB16</td><td colspan="2">CAR T CELL THERAPY: FULL SPEED AHEAD<br>R.J. Brentjens, New York, NY (USA)</td></tr><tr><td>EB17</td><td colspan="2">NEW DRUGS FOR OLD TARGETS<br>G. Salles, Lyon (France)</td></tr><tr><td>EB18</td><td colspan="2">NEW DRUGS FOR NEW TARGETS<br>A. Younes, New York, NY (USA)</td></tr></tbody></table>
<table><thead><tr><th></th><th>Abstract Nr</th><th>POSTER SESSION</th></tr></thead><tbody><tr><td>12:00-17:00<br>Marquee</td><td>136-159</td><td>BIOLOGY AND PATHOLOGY</td></tr><tr><td></td><td>160-169</td><td>CLL</td></tr><tr><td></td><td>170-183</td><td>INDOLENT LYMPHOMAS</td></tr><tr><td></td><td>184-191</td><td>MANTLE CELL LYMPHOMAS</td></tr><tr><td></td><td>192-206</td><td>AGGRESSIVE LYMPHOMAS</td></tr><tr><td></td><td>207-217</td><td>EXTRANODAL LYMPHOMAS</td></tr><tr><td></td><td>218-233</td><td>PTCL AND NK/T CELL LYMPHOMAS</td></tr><tr><td></td><td>234-245</td><td>HODGKIN LYMPHOMAS</td></tr><tr><td></td><td>246-262</td><td>IMMUNOTHERAPY</td></tr><tr><td></td><td>263-285</td><td>NOVEL TREATMENTS</td></tr><tr><td>12:00-13:00<br>Marquee</td><td></td><td>LUNCH TIME AND POSTER VIEWING</td></tr><tr><td>13:00-14:00<br>Room A, B, Marquee,<br>Cinema Corso, Auditorium and<br>Aula Magna (USI Università)</td><td></td><td>OPENING OF THE CONFERENCE 🌐<br>WELCOME AND INTRODUCTORY REMARKS<br>F. Cavalli, Bellinzona (Switzerland)<br>HENRY KAPLAN MEMORIAL LECTURE AND SAN SALVATORE FOUNDATION PRIZE 🌐<br>Introduction to San Salvatore Foundation: S. Coduri, Lugano (Switzerland)<br>Laudatio: R. Stahel, Zurich (Switzerland)</td></tr><tr><td></td><td>001</td><td>NEXT GENERATION CAR T CELLS FOR LYMPHOMA AND BEYOND<br>C.H. June, Philadelphia, PA (USA)</td></tr><tr><td>14:00-15:25<br>Room A, B, Marquee,<br>Cinema Corso, Auditorium and<br>Aula Magna (USI Università)</td><td></td><td>PLENARY SESSION<br>Co-chairs: J.O. Armitage, Omaha, NE (USA) and F. Cavalli, Bellinzona (Switzerland)</td></tr><tr><td>14:00</td><td>004</td><td>IDENTIFYING MUTATIONS ENRICHED IN RELAPSED-REFRACTORY DLBCL TO DERIVE GENETIC FACTORS UNDERLYING TREATMENT RESISTANCE<br>C. Rushton, Burnaby, B. C (Canada)</td></tr><tr><td>14:15</td><td>005</td><td>ROBUST: FIRST REPORT OF PHASE III RANDOMIZED STUDY OF LENALIDOMIDE/R-CHOP (R2-CHOP) VS PLACEBO/R-CHOP IN PREVIOUSLY UNTREATED ABC-TYPE DIFFUSE LARGE B-CELL LYMPHOMA<br>U. Vitolo, Turin (Italy)</td></tr><tr><td>14:30</td><td>006</td><td>ADDITION OF LENALIDOMIDE TO R-CHOP (R2CHOP) IMPROVES OUTCOMES IN NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): FIRST REPORT OF ECOG-ACRIN1412 A RANDOMIZED PHASE 2 US INTERGROUP STUDY OF R2CHOP VS R-CHOP<br>G.S. Nowakowski, Rochester, MN (USA)</td></tr><tr><td>14:45</td><td></td><td>Discussant for presentations 004, 005 and 006: M.A. Shipp, Boston, MA (USA)</td></tr><tr><td>15:00</td><td>007</td><td>IBRUTINIB VERSUS PLACEBO IN PATIENTS WITH ASYMPTOMATIC, TREATMENT-NAÏVE EARLY STAGE CLL: PRIMARY ENDPOINT RESULTS OF THE PHASE 3 DOUBLE-BLIND RANDOMIZED CLL12 TRIAL<br>P. Langerbeins, Cologne (Germany)</td></tr><tr><td>15:15</td><td></td><td>Discussant for presentation 007: S.M. O'Brien, Irvine, CA (USA)</td></tr><tr><td>15:25-15:50<br>Marquee</td><td></td><td>COFFEE BREAK</td></tr><tr><td>15:50-16:50<br>Room A, B, Marquee,<br>Cinema Corso, Auditorium and<br>Aula Magna (USI Università)</td><td></td><td>AACR-ICML JOINT SESSION - THE ROLE OF NON-CLINICAL MODELS AS BRIDGES TO EARLY CLINICAL TRIALS<br>Co-chairs: M. Foti, Philadelphia, PA (USA) and B. Nadel, Marseille (France)</td></tr><tr><td>15:50</td><td>008</td><td>DESIGNER ORGANOIDS FOR MODELING EPIGENETICS, SIGNALING, AND THERAPIES IN LYMPHOMA<br>A. Singh, New York, NY (USA)</td></tr></tbody></table>
<table><tr><td>16:10</td><td>009</td><td>MOUSE PDX AS NON-CLINICAL MODELS FOR LYMPHOMA<br/>A. Louissaint, Boston, MA (USA)</td></tr><tr><td>16:30</td><td>010</td><td>ADVANCING OUR UNDERSTANDING AND TREATMENT OF LYMPHOMA WITH<br/>SPONTANEOUS CANINE MODELS<br/>L. Aresu, Turin (Italy)</td></tr><tr><td>17:05-18:05</td><td></td><td>"FOCUS ON ..." SESSIONS<br/>5 parallel sessions</td></tr><tr><td>Room A</td><td></td><td>MANTLE CELL LYMPHOMA<br/>Chair: J.P. Leonard, New York, NY (USA)</td></tr><tr><td>17:05</td><td>011</td><td>COMBINATION OF IBRUTINIB WITH RITUXIMAB (IR) IS HIGHLY EFFECTIVE IN PREVIOUSLY<br/>UNTREATED ELDERLY (&gt;65 YEARS) PATIENTS (PTS) WITH MANTLE CELL LYMPHOMA (MCL)-<br/>PHASE II TRIAL<br/>P. Jain, Houston, TX (USA)</td></tr><tr><td>17:15</td><td>012</td><td>IBRUTINIB WITH RITUXIMAB (IR) AND SHORT COURSE R-HYPERCVAD/MTX IS VERY<br/>EFFICACIOUS IN PREVIOUSLY UNTREATED YOUNG PTS WITH MANTLE CELL LYMPHOMA<br/>(MCL)<br/>M. Wang, Houston, TX (USA)</td></tr><tr><td>17:25</td><td>013</td><td>AUTOLOGOUS STEM CELL TRANSPLANTATION IN FIRST REMISSION SIGNIFICANTLY<br/>PROLONGS PROGRESSION-FREE AND OVERALL SURVIVAL IN MANTLE CELL LYMPHOMA<br/>A. Zoellner, Munich (Germany)</td></tr><tr><td>17:35</td><td>014</td><td>OBINUTUZUMAB PLUS DHAP FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANTATION<br/>(ASCT) PLUS OBINUTUZUMAB MAINTENANCE PROVIDES A HIGH MRD RESPONSE RATE IN<br/>UNTREATED MCL PATIENTS, RESULTS OF LYMA-101 TRIAL, A LYSA GROUP STUDY<br/>S. Le Gouill, Nantes (France)</td></tr><tr><td>17:45</td><td>015</td><td>ZANUBRUTINIB IN PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA<br/>Y. Song, Beijing (China)</td></tr><tr><td>17:55</td><td>016</td><td>OUTCOMES IN FIRST RELAPSED-REFRACTORY YOUNGER PATIENTS WITH MANTLE CELL<br/>LYMPHOMA: RESULTS FROM THE MANTLE-FIRST STUDY<br/>C. Visco, Verona (Italy)</td></tr><tr><td>Room B</td><td></td><td>PET IMAGING<br/>Chair: B.D. Cheson, Washington, D.C. (USA)</td></tr><tr><td>17:05</td><td>017</td><td>A GENE EXPRESSION-BASED SCORE TO PREDICT INTERIM PET POSITIVITY IN HODGKIN<br/>LYMPHOMA PATIENTS TREATED WITH ABVD<br/>B. Donati, Reggio Emilia (Italy)</td></tr><tr><td>17:15</td><td>018</td><td>PERSISTENT MEDIASTINAL POSITRON EMISSION TOMOGRAPHY (PET)-POSITIVITY AFTER<br/>FRONTLINE THERAPY FOR HODGKIN LYMPHOMA IS BEST MANAGED BY CLOSE<br/>OBSERVATION<br/>M. Novo, Rochester, MN (USA)</td></tr><tr><td>17:25</td><td>019</td><td>HIGH TOTAL METABOLIC TUMOR VOLUME AT BASELINE ALLOWS TO DISCRIMINATE FOR<br/>SURVIVAL PATIENTS IN RESPONSE AFTER R-CHOP: AN ANCILLARY ANALYSIS OF THE<br/>REMARK STUDY<br/>L. Vercellino, Paris (France)</td></tr><tr><td>17:35</td><td>020</td><td>BASELINE TOTAL METABOLIC TUMOR VOLUME IS HIGHLY PROGNOSTIC FOR<br/>REFRACTORINESS TO IMMUNOCHEMOTHERAPY IN DLBCL: AN ANALYSIS OF THE PHASE<br/>3 GOYA TRIAL<br/>M. Trněný, Prague (Czech Republic)</td></tr><tr><td>17:45</td><td>021</td><td>RADIOMICS INCREASE THE PROGNOSTIC VALUE OF CLINICAL AND PET RISK FACTORS IN<br/>DLBCL: RESULTS FROM THE PHASE 3 GOYA STUDY<br/>S. Chauvie, Cuneo (Italy)</td></tr><tr><td>17:55</td><td>022</td><td>PROGNOSTIC VALUE OF PRE-TREATMENT PET SCAN IN PATIENTS WITH FOLLICULAR<br/>LYMPHOMA RECEIVING FRONTLINE THERAPY<br/>P. Strati, Houston, TX (USA)</td></tr></table>

(Continues)
<table><thead><tr><th></th><th></th><th></th><th></th></tr></thead><tbody><tr><td>Cinema Corso</td><td></td><td>PEDIATRIC LYMPHOMA</td><td></td></tr><tr><td></td><td></td><td>Chair: W. Wössmann, Hamburg (Germany)</td><td></td></tr><tr><td>17:05</td><td>023</td><td>NON-HODGKIN LYMPHOMA IN ADOLESCENT AND YOUNG ADULTS - A NATIONAL PROSPECTIVE POPULATION-BASED STUDY</td><td></td></tr><tr><td></td><td></td><td>R. Carr, London (UK)</td><td></td></tr><tr><td>17:15</td><td>024</td><td>INCLUSION OF A PEDIATRIC PERSPECTIVE INTO RECOMMENDATIONS FOR THE INITIAL EVALUATION AND STAGING OF HODGKIN LYMPHOMA: A CALL TO ACTION FROM THE INTERNATIONAL SEARCH WORKING GROUP</td><td></td></tr><tr><td></td><td></td><td>J. Flerlage, Memphis, TN (USA)</td><td></td></tr><tr><td>17:25</td><td>025</td><td>SAFETY AND RESPONSE AFTER 2 CYCLES OF BRENTUXIMAB VEDOTIN SUBSTITUTING VINCRISTINE IN THE OEPA/COPDAC REGIMEN FOR HIGH RISK PEDIATRIC HODGKIN LYMPHOMA (HL)</td><td></td></tr><tr><td></td><td></td><td>J. Flerlage, Memphis, TN (USA)</td><td></td></tr><tr><td>17:35</td><td>026</td><td>RESPONSE-ADAPTED TREATMENT WITH NIVOLUMAB AND BRENTUXIMAB VEDOTIN IN YOUNG PATIENTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA: CHECKMATE 744 SUBGROUP ANALYSES</td><td></td></tr><tr><td></td><td></td><td>K.M. Kelly, Buffalo, NY (USA)</td><td></td></tr><tr><td>17:45</td><td>027</td><td>IBRUTINIB + CHEMOIMMUNOTHERAPY (CIT) FOR RELAPSED/REFRACTORY MATURE B-CELL NON-HODGKIN LYMPHOMA (B-NHL) IN CHILDREN (SPARKLE TRIAL): INITIAL SAFETY, PK, AND EFFICACY</td><td></td></tr><tr><td></td><td></td><td>A. Burke, Cambridge (UK)</td><td></td></tr><tr><td>17:55</td><td>028</td><td>CHIMERIC ANTIGEN RECEPTOR T-CELLS (CAR-T) FOR REFRACTORY AND RELAPSED BURKITT'S LYMPHOMA, EARLY RESPONSE IN PEDIATRIC PATIENTS</td><td></td></tr><tr><td></td><td></td><td>W.Q. Zhang, Beijing (China)</td><td></td></tr><tr><td>Auditorium (USI Università)</td><td></td><td>RESULTS FROM SINGLE AGENT TRIALS</td><td></td></tr><tr><td></td><td></td><td>Chair: C. Thieblemont, Paris (France)</td><td></td></tr><tr><td>17:05</td><td>029</td><td>PHASE 2 STUDY OF ACALABRUTINIB IN IBRUTINIB-INTOLERANT PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA</td><td></td></tr><tr><td></td><td></td><td>K.A. Rogers, Columbus, OH (USA)</td><td></td></tr><tr><td>17:15</td><td>030</td><td>RAPID AND DURABLE RESPONSES WITH THE SYK/JAK INHIBITOR CERDULATINIB IN A PHASE 2 STUDY IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA-ALONE OR IN COMBINATION WITH RITUXIMAB</td><td></td></tr><tr><td></td><td></td><td>S.D. Smith, Seattle, WA (USA)</td><td></td></tr><tr><td>17:25</td><td>031</td><td>A PHASE 2B STUDY OF SELINEXOR IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)</td><td></td></tr><tr><td></td><td></td><td>N. Kalakonda, Liverpool (UK)</td><td></td></tr><tr><td>17:35</td><td>032</td><td>TIPIFARNIB IN RELAPSED OR REFRACTORY ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA (AITL) AND CXCL12+ PERIPHERAL T-CELL LYMPHOMA (PTCL): PRELIMINARY RESULTS FROM A PHASE 2 STUDY</td><td></td></tr><tr><td></td><td></td><td>T.E. Witzig, Rochester, MN (USA)</td><td></td></tr><tr><td>17:45</td><td>033</td><td>DUVELISIB, AN ORAL DUAL PI3K-δ,γ INHIBITOR, EFFICACY AND SAFETY IN PATIENTS WITH RELAPSED OR REFRACTORY (RR) PERIPHERAL T-CELL LYMPHOMA: RATIONALE FOR THE PHASE 2 PRIMO TRIAL</td><td></td></tr><tr><td></td><td></td><td>S.M. Horwitz, New York, NY (USA)</td><td></td></tr><tr><td>17:55</td><td>034</td><td>EFFICACY OF MOGAMULIZUMAB IN PREVIOUSLY TREATED PATIENTS WITH LESS ADVANCED MYCOSIS FUNGOIDES: RESULTS FROM THE MAJORIC STUDY</td><td></td></tr><tr><td></td><td></td><td>J. Scarisbrick, Birmingham (UK)</td><td></td></tr><tr><td>Aula Magna (USI Università)</td><td></td><td>ONGOING TRIALS</td><td></td></tr><tr><td></td><td></td><td>Chair: J.M. Vose, Omaha, NE (USA)</td><td></td></tr><tr><td>17:05</td><td>OT01</td><td>NCRI PETREA TRIAL: A PHASE 3 EVALUATION OF PET-GUIDED, RESPONSE-ADAPTED THERAPY IN PATIENTS WITH PREVIOUSLY UNTREATED, ADVANCED-STAGE, HIGH-TUMOUR-BURDEN FOLLICULAR LYMPHOMA</td><td></td></tr><tr><td></td><td></td><td>A.R. Pettitt, Liverpool (UK)</td><td></td></tr></tbody></table>
<table><tr><td>17:15</td><td>OT02</td><td>POLARIX: A PHASE 3 STUDY OF POLATUZUMAB VEDOTIN (POLA) PLUS R-CHP VERSUS R-CHOP IN PATIENTS (PTS) WITH UNTREATED DLBCL<br/>H. Tilly, Rouen (France)</td></tr><tr><td>17:25</td><td>OT03</td><td>PHASE III RANDOMIZED STUDY OF ENZASTAURIN/R-CHOP VS PLACEBO/R-CHOP IN FRONTLINE HIGH RISK DIFFUSE LARGE B CELL LYMPHOMA PATIENTS WITH GENOMIC BIOMARKER DGM1 (ENGINE STUDY)<br/>Y. Xie, Beijing (China)</td></tr><tr><td>17:35</td><td>OT04</td><td>THE DIAL STUDY (DUAL IMMUNOMODULATION IN AGGRESSIVE LYMPHOMA): RANDOMIZED PHASE 2 TRIAL OF VARLILUMAB PLUS NIVOLUMAB IN RELAPSED/REFRACTORY AGGRESSIVE B-CELL LYMPHOMAS<br/>J.C. Villasboas, Rochester, MN (USA)</td></tr><tr><td>17:45</td><td>OT05</td><td>ACCEPT: A PHASE IB/II COMBINATION OF ACALABRUTINIB WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE AND PREDNISOLONE (R-CHOP) FOR PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)<br/>T. Cummin, Southampton (UK)</td></tr><tr><td>17:55</td><td>OT06</td><td>TELLOMAK: T-CELL LYMPHOMA ANTI-KIR3DL2 THERAPY: AN OPEN LABEL, MULTI-COHORT, MULTI-CENTER, INTERNATIONAL PHASE II STUDY EVALUATING THE EFFICACY AND SAFETY OF IPH4102 ALONE OR IN COMBINATION WITH CHEMOTHERAPY IN PATIENTS WITH ADVANCED T-CELL LYMPHOMA<br/>P. Porcu, Philadelphia, PA (USA)</td></tr></table>

Thursday, June 20, 2019

<table><tr><td>08:00-08:45</td><td></td><td>MEET THE PROFESSOR SESSIONS 🏫<br/>5 parallel sessions</td></tr><tr><td>Room A</td><td>EB10</td><td>THE MODERN APPROACH TO MANTLE CELL LYMPHOMA<br/>S. Rule, Plymouth (UK)</td></tr><tr><td>Room B</td><td>EB09</td><td>MULTIPLE MYELOMA: EVERY YEAR A NEW STANDARD?<br/>S.V. Rajkumar, Rochester, MN (USA)</td></tr><tr><td>Cinema Corso</td><td>EB01</td><td>PCNSL, A CURABLE DISEASE<br/>T.T. Batchelor, Boston, MA (USA)</td></tr><tr><td>Auditorium<br/>(USI Università)</td><td>EB11</td><td>LIQUID BIOPSY IN NON-HODGKIN'S LYMPHOMA<br/>W.H. Wilson, Bethesda, MD (USA)</td></tr><tr><td>Aula Magna<br/>(USI Università)</td><td>EB04</td><td>NEW TREATMENT OPTIONS IN HAIRY CELL LEUKEMIA WITH FOCUS ON BRAF INHIBITORS<br/>B. Falini, Perugia (Italy)<br/>offered only once</td></tr><tr><td>09:00-17.00<br/>Marquee</td><td></td><td>POSTER SESSION</td></tr><tr><td>09:00-10:30</td><td></td><td>"CASE DISCUSSION" SESSIONS: Spain vs Texas (USA)<br/>4 parallel sessions</td></tr><tr><td>Room A</td><td></td><td>DLBCL<br/>Chair: L.H. Sehn, Vancouver, B.C. (Canada)<br/>Discussants: E. Giné Soca, Barcelona vs J.R. Westin, Houston</td></tr><tr><td>Cinema Corso</td><td></td><td>HODGKIN LYMPHOMA<br/>Chair: A.S. LaCasce, Boston, MA (USA)<br/>Discussants: A.M. Sureda Balari, Barcelona vs H.J. Lee, Houston</td></tr><tr><td>Auditorium<br/>(USI Università)</td><td></td><td>RADIOTHERAPY FOR LYMPHOMAS<br/>Chair: L. Specht, Copenhagen (Denmark)<br/>Discussants: T. Illidge, Manchester (UK) vs B.S. Dabaja, Houston</td></tr><tr><td>Aula Magna<br/>(USI Università)</td><td></td><td>DIFFICULT PATHOLOGICAL CASES<br/>Chair: M. Ghielmini, Bellinzona (Switzerland)<br/>Presenters: E. Campo, Barcelona (Spain), S. Dirnhofer, Basel (Switzerland) and P. Gaulard, Paris (France)<br/>Discussants: A. Lopez-Guillermo, Barcelona vs R. Hagemeister, Houston</td></tr></table>
<table><thead><tr><th></th><th></th><th></th><th></th></tr></thead><tbody><tr><td>09:00-10:30<br>Room B<br>and Marquee</td><td>Abstract Nr</td><td>SESSION 1 - DLBCL: BIOLOGY</td><td>Co-chairs: R. Dalla-Favera, New York, NY (USA) and R. Küppers, Essen (Germany)</td></tr><tr><td>09:00</td><td>035</td><td>AN AUTOCHTHONOUS MOUSE MODEL OF MYD88 P.L265P- AND BCL2-DRIVEN DIFFUSE LARGE B CELL LYMPHOMA</td><td>G. Knittel, Cologne (Germany)</td></tr><tr><td>09:15</td><td>036</td><td>CRYPTIC MYC AND BCL2 REARRANGEMENTS ARE AMONG A RANGE OF GENETIC MECHANISMS UNDERLYING THE DOUBLE HIT SIGNATURE IN NON-DOUBLE HIT DIFFUSE LARGE B-CELL LYMPHOMA</td><td>L.K. Hilton, Burnaby, B.C. (Canada)</td></tr><tr><td>09:30</td><td>037</td><td>FUNCTIONAL CHARACTERIZATION OF NFKBIZ 3' UTR MUTATIONS IN DIFFUSE LARGE B-CELL LYMPHOMA</td><td>S.E. Arthur, Burnaby, B.C. (Canada)</td></tr><tr><td>09:45</td><td>038</td><td>THE TRANSCRIPTION FACTOR FLI1 SUSTAINS RELEVANT BIOLOGICAL PATHWAYS AND DRIVES ONCOGENES THAT PROMOTE CELL GROWTH IN DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)</td><td>G. Sartori, Bellinzona (Switzerland)</td></tr><tr><td>10:00</td><td>039</td><td>TRANSCRIPTIONAL AND GENOMIC INTRA-TUMOR HETEROGENEITY DRIVES SUBCLONE SPECIFIC DRUG RESPONSES IN DIFFUSE LARGE B CELL LYMPHOMA</td><td>T. Roider, Heidelberg (Germany)</td></tr><tr><td>10:15</td><td>040</td><td>THE NONCODING RNA GECPAR IS INVOLVED IN WNT SIGNALING AND HAS TUMOR-SUPPRESSOR ACTIVITY IN DIFFUSE LARGE B CELL LYMPHOMA</td><td>S. Napoli, Bellinzona (Switzerland)</td></tr><tr><td>10:30-11:00<br>Marquee, Cinema Corso<br>and USI Università</td><td></td><td>COFFEE BREAK</td><td></td></tr><tr><td>11:00-12:00<br>Room A, B, Marquee,<br>Cinema Corso, Auditorium<br>and Aula Magna (USI Università)</td><td></td><td>SESSION 2 - DLBCL: CLINICAL DATA</td><td>Co-chairs: M. Trněný, Prague (Czech Republic) and W. Zhao, Shanghai (China)</td></tr><tr><td>11:00</td><td>041</td><td>INTEGRATION BETWEEN METABOLIC TUMOUR VOLUME AND METABOLIC HETEROGENEITY PREDICTS OUTCOME OF DLBCL LYMPHOMA PATIENTS IN THE SAKK 38/07 STUDY COHORT</td><td>L. Ceriani, Bellinzona (Switzerland)</td></tr><tr><td>11:15</td><td>042</td><td>SMART START: RITUXIMAB, LENALIDOMIDE, AND IBRUTINIB ALONE PRIOR TO COMBINATION WITH CHEMOTHERAPY FOR PATIENTS WITH NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA</td><td>J.R. Westin, Houston, TX (USA)</td></tr><tr><td>11:30</td><td>043</td><td>RITUXIMAB MAINTENANCE FOR PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA IN FIRST COMPLETE REMISSION: RESULTS FROM A RANDOMIZED HOVON-NORDIC LYMPHOMA GROUP PHASE III STUDY</td><td>P. Lugtenburg, Rotterdam (Netherlands)</td></tr><tr><td>11:45</td><td>044</td><td>IMPAIRED IMMUNE HEALTH IN SURVIVORS OF DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): A LARGE POPULATION-BASED STUDY</td><td>T. Shree, Stanford, CA (USA)</td></tr><tr><td>12:00-13:00<br>Marquee</td><td></td><td>LUNCH TIME AND POSTER VIEWING</td><td>from 12:30 to 13:00 authors in front of their poster for discussion with attendees</td></tr><tr><td>12:00-13:00<br>Room E</td><td></td><td>15-ICML PRESS CONFERENCE</td><td></td></tr><tr><td>13:00-13:45<br>Room A, B, Marquee,<br>Cinema Corso and Aula<br>Magna (USI Università)</td><td></td><td>GIANNI BONADONNA MEMORIAL LECTURE</td><td>sponsored by the American Association for Cancer Research-AACR</td></tr><tr><td></td><td></td><td>Laudatio: M.A. Shipp, Boston, MA (USA)</td><td></td></tr><tr><td></td><td>002</td><td>PRECISION EPIGENETIC THERAPY FOR B-CELL LYMPHOMA</td><td>A.M. Melnick, New York, NY (USA)</td></tr></tbody></table>
<table><tr><td>13:45-15:15<br>Room A, B, Marquee, Cinema Corso, Auditorium and Aula Magna (USI Università)</td><td>045</td><td>INTERNATIONAL PROGNOSTIC SCORE FOR EARLY STAGE CHRONIC LYMPHOCYTIC LEUKEMIA (IPS-A)<br>A. Condoluci, Bellinzona (Switzerland)</td></tr><tr><td>14:00</td><td>046</td><td>FIXED-DURATION VENETOCLAX PLUS OBINUTUZUMAB IMPROVES PFS AND MINIMAL RESIDUAL DISEASE NEGATIVITY IN PATIENTS WITH PREVIOUSLY UNTREATED CLL AND COMORBIDITIES<br>K. Fischer, Cologne (Germany)</td></tr><tr><td>14:15</td><td>047</td><td>GENETIC MARKERS AND OUTCOME IN THE CLL14 TRIAL OF THE GCLLSG COMPARING FRONT LINE OBINUTUZUMAB PLUS CHLORABMUCIL OR VENETOCLAX IN PATIENTS WITH COMORBIDITY<br>E. Tausch, Ulm (Germany) Best abstract submitted by a young investigator / travel grant recipient</td></tr><tr><td>14:30</td><td>048</td><td>ACALABRUTINIB VS RITUXIMAB PLUS IDELALISIB (IR) OR BENDAMUSTINE (BR) BY INVESTIGATOR CHOICE IN RELAPSED/REFRACTORY (R/R) CHRONIC LYMPHOCYTIC LEUKEMIA: PHASE 3 ASCEND STUDY<br>P. Ghia, Milan (Italy)</td></tr><tr><td>14:45</td><td>049</td><td>ZANUBRUTINIB FOR PATIENTS WITH RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA<br>W. Xu, Nanjing (China)</td></tr><tr><td>15:00</td><td>050</td><td>A PHASE 2 STUDY TO ASSESS THE SAFETY AND EFFICACY OF UMBRALISIB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) WHO ARE INTOLERANT TO PRIOR BTK OR PI3K DELTA INHIBITOR THERAPY<br>A.R. Mato, New York, NY (USA)</td></tr><tr><td>15:15-15:40<br>Marquee</td><td></td><td>COFFEE BREAK</td></tr><tr><td>15:40-16:55</td><td></td><td>2 parallel sessions</td></tr><tr><td>Room A, Cinema Corso<br>Auditorium and Aula<br>Magna (USI Università)</td><td>051</td><td>SESSION 4 - TREATMENT WITH NOVEL ANTIBODIES<br>Co-chairs: D.G. Maloney, Seattle, WA (USA) and P.L. Zinzani, Bologna (Italy)</td></tr><tr><td>15:40</td><td>051</td><td>THE FIRST-IN-CLASS ANTI-CD47 ANTIBODY HU5F9-G4 + RITUXIMAB INDUCES DURABLE RESPONSES IN RELAPSED/REFRACTORY DLBCL AND INDOLENT LYMPHOMA: INTERIM PHASE 1B/2 RESULTS<br>R.H. Advani, Stanford, CA (USA)</td></tr><tr><td>15:55</td><td>052</td><td>CLINICAL ACTIVITY OF REGN1979, AN ANTI-CD20 X ANTI-CD3 BISPECIFIC ANTIBODY (AB) IN PATIENTS (PTS) WITH (W/) RELAPSED/REFRACTORY (R/R) B-CELL NON-HODGKIN LYMPHOMA (B-NHL)<br>M.S. Topp, Würzburg (Germany)</td></tr><tr><td>16:10</td><td>053</td><td>CD20-TCB (RG6026), A NOVEL "2:1" FORMAT T-CELL-ENGAGING BISPECIFIC ANTIBODY, INDUCES COMPLETE REMISSIONS IN RELAPSED/REFRACTORY B-CELL NON-HODGKIN'S LYMPHOMA<br>M.J. Dickinson, Melbourne (Australia)</td></tr><tr><td>16:25</td><td>054</td><td>ANALYSIS OF EFFICACY AND SAFETY OF LONCASTUXIMAB TESIRINE (ADCT-402) BY DEMOGRAPHIC AND CLINICAL CHARACTERISTICS IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA<br>J. Radford, Manchester (UK)</td></tr><tr><td>16:40</td><td>055</td><td>ANALYSIS OF CLINICAL DETERMINANTS DRIVING SAFETY AND EFFICACY OF CAMIDANLUMAB TESIRINE (ADCT-301, CAMI) IN RELAPSED/REFRACTORY (R/R) CLASSICAL HODGKIN LYMPHOMA (CHL)<br>G. Collins, Oxford (UK)</td></tr></table>
<table><tbody><tr><td>15:40-16:55<br>Room B and Marquee</td><td></td><td><strong>SESSION 5 - T-CELL LYMPHOMAS</strong><br>Co-chairs: S. Luminari, Reggio Emilia (Italy) and K.J. Savage, Vancouver, B.C. (Canada)</td></tr><tr><td>15:40</td><td>056</td><td>RISK OF BREAST IMPLANT ASSOCIATED ANAPLASTIC LARGE CELL LYMPHOMA (BIA-ALCL) IN A COHORT OF 3546 WOMEN PROSPECTIVELY FOLLOWED AFTER RECEIVING TEXTURED BREAST IMPLANTS.<br>P. Ghione, New York, NY (USA)</td></tr><tr><td>15:55</td><td>057</td><td>AUTOLOGOUS STEM CELL TRANSPLANTATION AS PART OF FIRST-LINE THERAPY IN PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA: A MULTICENTER GELTAMO/FIL STUDY<br>M. Lopez-Parra, Salamanca (Spain)</td></tr><tr><td>16:10</td><td>058</td><td>FIRST-LINE THERAPY OF T-CELL LYMPHOMA: ALLOGENEIC OR AUTOLOGOUS TRANSPLANTATION FOR CONSOLIDATION - FINAL RESULTS OF THE AATT STUDY<br>O. Tournilhac, Clermont-Ferrand (France)</td></tr><tr><td>16:25</td><td>059</td><td>TREATMENT BENEFIT ASSOCIATING WITH NON-ANTHRACYCLINE CHEMOTHERAPY IN EXTRANODAL NK/T-CELL LYMPHOMA, NASAL TYPE<br>S. Qi, Beijing (China)</td></tr><tr><td>16:40</td><td>060</td><td>SINTILIMAB FOR RELAPSED/REFRACTORY (R/R) EXTRANODAL NK/T CELL LYMPHOMA (ENKTL): A MULTICENTER, SINGLE-ARM, PHASE 2 TRIAL (ORIENT-4)<br>R. Tao, Shanghai (China)</td></tr><tr><td>17:05-18:05</td><td></td><td><strong>"FOCUS ON ..." SESSIONS</strong><br>5 parallel sessions</td></tr><tr><td>Room A</td><td></td><td><strong>CLL AND MORE</strong><br>Chair: D. Rossi, Bellinzona (Switzerland)</td></tr><tr><td>17:05</td><td>061</td><td>FIVE-YEAR FOLLOW-UP OF FIRST-LINE IBRUTINIB FOR TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA//SMALL LYMPHOCYTIC LYMPHOMA<br>A. Tedeschi, Milan (Italy)</td></tr><tr><td>17:15</td><td>062</td><td>HIGH EFFICACY OF VENETOCLAX PLUS OBINUTUZUMAB IN PATIENTS WITH COMPLEX KARYOTYPE (CKT) AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A PROSPECTIVE ANALYSIS FROM THE CLL14 TRIAL<br>O. Al-Sawaf, Cologne (Germany)</td></tr><tr><td>17:25</td><td>063</td><td>IMPACT OF MAJOR GENOMIC ALTERATIONS ON OUTCOME OF RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS RECEIVING VENETOCLAX PLUS RITUXIMAB IN THE PHASE 3 MURANO STUDY<br>J. Wu, San Francisco, CA (USA)</td></tr><tr><td>17:35</td><td>064</td><td>AN UNDETECTABLE PB MRD STATUS SHOULD BE THE THERAPEUTIC GOAL WITH VENETOCLAX THERAPY IN RELAPSED/REFRACTORY CLL<br>S. Handunnetti, Melbourne (Australia)</td></tr><tr><td>17:45</td><td>065</td><td>TRANSCEND CLL 004: MINIMAL RESIDUAL DISEASE AFTER LISOCABTAGENE MARALEUCEL IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA<br>T. Siddiqi, Duarte, CA (USA)</td></tr><tr><td>17:55</td><td>066</td><td>THE BRAF INHIBITOR VEMURAFENIB PLUS RITUXIMAB PRODUCES A HIGH RATE OF DEEP AND DURABLE RESPONSES IN RELAPSED/REFRACTORY HAIRY CELL LEUKEMIA: UPDATED RESULTS OF A PHASE-2 TRIAL<br>E. Tiacci, Perugia (Italy)</td></tr><tr><td>Room B</td><td></td><td><strong>CHEMOTHERAPY-FREE STRATEGIES</strong><br>Chair: J.W. Friedberg, Rochester, NY (USA)</td></tr><tr><td>17:05</td><td>067</td><td>PREDICTIVE VALUE OF POD24 VALIDATION IN FOLLICULAR LYMPHOMA PATIENTS INITIALLY TREATED WITH CHEMOTHERAPY-FREE REGIMENS IN A POOLED ANALYSIS OF THREE RANDOMIZED TRIALS OF THE SWISS GROUP FOR CLINICAL CANCER RESEARCH (SAKK)<br>A. Moccia, Bellinzona (Switzerland)</td></tr><tr><td>17:15</td><td>068</td><td>EFFICACY AND SAFETY OF OBINUTUZUMAB + LENALIDOMIDE + ATEZOLIZUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA: PRIMARY ANALYSIS OF A PHASE 1B/2 TRIAL<br>F. Morschhauser, Lille (France)</td></tr></tbody></table>
<table><tr><td>17:25</td><td>069</td><td>AUGMENT PHASE III STUDY: LENALIDOMIDE/RITUXIMAB (R2) IMPROVED EFFICACY OVER RITUXIMAB/PLACEBO IN RELAPSED/REFRACTORY FOLLICULAR PATIENTS IRRESPECTIVE OF POD24 STATUS<br>J.P. Leonard, New York, NY (USA)</td></tr><tr><td>17:35</td><td>070</td><td>INTERIM ANALYSIS OF PHASE IIIB MAGNIFY STUDY OF INDUCTION R2 FOLLOWED BY MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NON-HODGKIN LYMPHOMA<br>J. Sharman, Eugene, OR (USA)</td></tr><tr><td>17:45</td><td>071</td><td>RITUXIMAB PLUS LENALIDOMIDE IS AS EFFECTIVE AS IMMUNOCHEMOTHERAPY IN THE ERADICATION OF MOLECULAR DISEASE IN UNTREATED FOLLICULAR LYMPHOMA: RELEVANCE LYSA ANCILLARY STUDY<br>M.H. Delfau-Larue, Creteil (France)</td></tr><tr><td>17:55</td><td>072</td><td>SAKK 35/15: A PHASE I TRIAL OF OBINUTUZUMAB IN COMBINATION WITH VENETOCLAX IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA PATIENTS.<br>A. Stathis, Bellinzona (Switzerland)</td></tr><tr><td>Cinema Corso</td><td></td><td><strong>NON-CLINICAL AND EARLY CLINICAL DATA WITH NEW COMBINATIONS</strong><br>Chair: A. Davies, Southampton (UK)</td></tr><tr><td>17:05</td><td>073</td><td>PHASE I/II STUDY OF UMBRALISIB (TGR-1202) IN COMBINATION WITH UBLITUXIMAB (TG-1101) AND PEMBROLIZUMAB IN PATIENTS WITH REL/REF CLL AND RICHTER'S TRANSFORMATION<br>A.R. Mato, New York, NY (USA)</td></tr><tr><td>17:15</td><td>074</td><td>PEMBROLIZUMAB WITH RCHOP IN PREVIOUSLY UNTREATED DIFFUSE LARGE B-CELL AND GRADE 3B FOLLICULAR LYMPHOMA: FINAL RESULTS OF A PHASE I TRIAL<br>S.D. Smith, Seattle, WA (USA)</td></tr><tr><td>17:25</td><td>075</td><td>ZANUBRUTINIB PLUS OBINUTUZUMAB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL) OR RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL)<br>C.S. Tam, Melbourne (Australia)</td></tr><tr><td>17:35</td><td>076</td><td>A PHASE I/II TRIAL OF IBRUTINIB, INTRATUMORAL CPG AND LOCAL RADIATION IN PATIENTS WITH LOW-GRADE B-CELL LYMPHOMA: INTERIM CLINICAL AND CORRELATIVE RESULTS<br>T. Shree, Stanford, CA (USA)</td></tr><tr><td>17:45</td><td>077</td><td>EXTENDED FOLLOW-UP OF A PHASE I TRIAL OF IPILIMUMAB, NIVOLUMAB AND BRENTUXIMAB VEDOTIN IN RELAPSED HODGKIN LYMPHOMA: A TRIAL OF THE ECOG-ACRIN RESEARCH GROUP (E4412)<br>C. Diefenbach, New York, NY (USA)</td></tr><tr><td>17:55</td><td>078</td><td>HIGH EXPRESSION OF BCL-2 AND BCL-XL IN DIFFUSE LARGE B-CELL LYMPHOMA CONFER POOR PROGNOSIS BUT MAY BE REVERSIBLE BY COMBINED INHIBITION WITH BET INHIBITORS AND BH3 MIMETICS.<br>T.E. Cummin, Southampton (UK)</td></tr><tr><td>Auditorium<br>(USI Università)</td><td></td><td><strong>NON-CLINICAL NEW DRUGS</strong><br>Chair: L. Pasqualucci, New York, NY (USA)</td></tr><tr><td>17:05</td><td>079</td><td>FIRST-IN-CLASS HAT ACTIVATOR HIGHLY SYNERGISTIC WITH PAN-HDAC INHIBITOR ROMIDEPSIN LEADING TO PROFOUND HISTONE ACETYLATION CYTOTOXICITY<br>Y. Liu, New York, NY (USA)</td></tr><tr><td>17:15</td><td>080</td><td>COPANLISIB AND VOLASERTIB OVERCOME IBRUTINIB-VENETOCLAX RESISTANCE VIA TARGETING PI3K-AKT SIGNALING AND G2/M CELL CYCLE TRANSITION IN MANTLE CELL LYMPHOMA<br>R. Zhang, Houston, TX (USA)</td></tr><tr><td>17:25</td><td>081</td><td>THE LANDSCAPE OF DRUG PERTUBATION EFFECTS IN LEUKEMIA AND LYMPHOMA<br>T. Zenz, Zurich (Switzerland)</td></tr><tr><td>17:35</td><td>082</td><td>DISCOVERY OF A NOVEL, POTENTIAL FIRST-IN-CLASS MALT1 PROTEASE INHIBITOR FOR THE TREATMENT OF B CELL LYMPHOMAS<br>U. Philippar, Bersee (Belgium)</td></tr></table>

(Continues)
<table><tr><td>17:45</td><td>083</td><td>KYM-001, A FIRST-IN-CLASS ORAL IRAK4 PROTEIN DEGRADER, INDUCES TUMOR REGRESSION IN XENOGRAFT MODELS OF MYD88-MUTANT ABC DLBCL ALONE AND IN COMBINATION WITH BTK INHIBITION<br/>J. Kelleher, Cambridge, MA (USA)</td></tr><tr><td>17:55</td><td>084</td><td>THE ANTIBODY-DRUG CONJUGATE (ADC) LONCASTUXIMAB TESIRINE (ADCT-402)<br/>TARGETING CD19 SHOWS STRONG in vitro ANTI-LYMPHOMA ACTIVITY BOTH AS SINGLE AGENTS AND IN COMBINATION<br/>C. Tarantelli, Bellinzona (Switzerland)</td></tr><tr><td>Aula Magna<br/>(USI Università)</td><td></td><td><strong>HIGH RISK LARGE B-CELL LYMPHOMAS</strong><br/>Chair: L.H. Sehn, Vancouver, B.C. (Canada)</td></tr><tr><td>17:05</td><td>085</td><td>EBV+ CNS LYMPHOMAS HAVE A DISTINCTIVE TUMOR MICROENVIRONMENT AND GENETIC PROFILE, WHICH IS AMENABLE TO COMBINATION 3RD PARTY EBV-SPECIFIC CTL AND IBRUTINIB THERAPY<br/>M.K. Gandhi, Brisbane (Australia)</td></tr><tr><td>17:15</td><td>086</td><td>YOUNG HIGH RISK PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA INCLUDING BCL-2/ MYC DOUBLE HIT LYMPHOMAS BENEFIT FROM DOSE-DENSE IMMUNOCHEMOTHERAPY WITH EARLY CNS PROPHYLAXIS<br/>S. Leppä, Helsinki (Finland)</td></tr><tr><td>17:25</td><td>087</td><td>SAFETY AND EFFICACY OF THE PD-L1 INHIBITOR DURVALUMAB WITH R-CHOP OR R2-CHOP IN SUBJECTS WITH PREVIOUSLY UNTREATED, HIGH-RISK DLBCL<br/>G.S. Nowakowski, Rochester, MN (USA)</td></tr><tr><td>17:35</td><td>088</td><td>INITIAL RESULTS OF A MULTICENTER PHASE 2 STUDY OF VENETOCLAX IN COMBINATION WITH DOSE-ADJUSTED R-EPOCH FOR PATIENTS WITH RICHTER'S SYNDROME (CRC-043)<br/>M.S. Davids, Boston, MA (USA)</td></tr><tr><td>17:45</td><td>089</td><td>IMPROVED OUTCOMES IN PATIENTS (PTS) WITH BCL2-POSITIVE DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) TREATED WITH VENETOCLAX (VEN) PLUS R-CHOP: RESULTS FROM THE PHASE 2 CAVALLI STUDY<br/>F. Morschhauser, Lille (France)</td></tr><tr><td>17:55</td><td>090</td><td>CD19-DIRECTED CAR T CELL THERAPY (CTL019) FOR RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL AND FOLLICULAR LYMPHOMAS: FOUR YEAR OUTCOMES<br/>E.A. Chong, Philadelphia, PA (USA)</td></tr></table>

Friday, June 21, 2019

<table><tr><td>08:00-08:45</td><td></td><td><strong>MEET THE PROFESSOR SESSIONS</strong><br/>5 parallel sessions</td></tr><tr><td>Room A</td><td>EB05</td><td>HOW TO APPROACH CLL IN CLINICAL PRACTICE<br/>M. Hallek, Cologne (Germany)</td></tr><tr><td>Room B</td><td>EB02</td><td>DOUBLE HIT LYMPHOMA, SO WHAT?<br/>A. Davies, Southampton (UK)</td></tr><tr><td>Cinema Corso</td><td>EB06</td><td>CUTANEOUS LYMPHOMAS<br/>W. Kempf, Zurich (Switzerland)</td></tr><tr><td>Auditorium<br/>(USI Università)</td><td>EB07</td><td>MANAGING THE TOXICITIES OF CAR T-CELL THERAPY<br/>S.S. Neelapu, Houston, TX (USA)</td></tr><tr><td>Aula Magna<br/>(USI Università)</td><td>EB08</td><td>RARE B CELL LYMPHOMAS IN CHILDREN AND ADOLESCENTS<br/>L. Quintanilla-Martinez de Fend, Tübingen (Germany) and<br/>W. Wössmann, Hamburg (Germany)<br/>offered only once</td></tr><tr><td>09:00-18:30<br/>Marquee</td><td></td><td><strong>POSTER SESSION</strong></td></tr><tr><td>09:00-10:30</td><td></td><td><strong>"CASE DISCUSSION" SESSIONS: Spain vs Texas (USA)</strong><br/>3 parallel sessions</td></tr><tr><td>Room A</td><td></td><td><strong>FL/INDOLENT LYMPHOMA</strong><br/>Chair: S. Rule, Plymouth (UK)<br/>Discussants: M. Provencio Pulla, Madrid vs L.J. Nastoupil, Houston</td></tr></table>
<table><tr><td>Cinema Corso</td><td></td><td>CLL<br>Chair: S.M. O'Brien, Irvine, CA (USA)<br>Discussants: J. Delgado, Barcelona vs P.A. Thompson, Houston</td></tr><tr><td>Aula Magna<br>(USI Università)</td><td></td><td>PTCL<br>Chair: K.J. Savage, Vancouver, B.C. (Canada)<br>Discussants: A. Martín, Salamanca vs N.H. Fowler, Houston</td></tr><tr><td>09:00-10:30<br>Room B and Marquee</td><td></td><td>SESSION 6 – LYMPHOMA PATHOLOGY<br>Co-chairs: K. Ohshima, Kurume (Japan) and E. Campo, Barcelona (Spain)</td></tr><tr><td>09:00</td><td>091</td><td>DIAGNOSIS AND CLASSIFICATION ASSISTANCE FROM LYMPHOMA MICROSCOPIC IMAGES<br>USING DEEP LEARNING<br>P. Brousset, Toulouse (France)</td></tr><tr><td>09:15</td><td>092</td><td>INTEGRATING TUMOR- AND MICROENVIRONMENT-REFLECTING GENES IN A UNIQUE AND<br>ROUTINE-APPLICABLE ASSAY FOR ACCURATE RISK PREDICTION IN DLBCL.<br>S.A. Pileri, Milan (Italy)</td></tr><tr><td>09:30</td><td>093</td><td>CONCORDANCE BETWEEN IMMUNOHISTOCHEMISTRY AND GENE EXPRESSION PROFILING<br>SUBTYPING FOR DIFFUSE LARGE B-CELL LYMPHOMA IN THE PHASE 3 PHOENIX TRIAL<br>S. Balasubramanian, San Diego CA (USA)</td></tr><tr><td>09:45</td><td>094</td><td>LONGITUDINAL ANALYSES OF DIAGNOSTIC-RELAPSE BIOPSIES OF DIFFUSE LARGE B CELL<br>LYMPHOMA SUGGEST THAT RELAPSE IS MEDIATED BY DISTINCT MECHANISMS IN ABC<br>AND GCB LYMPHOMA<br>S. Araf, London (UK)</td></tr><tr><td>10:00</td><td>095</td><td>DEFINING BURKITT-LIKE LYMPHOMA WITH 11Q ABERRATION IN A SPECIALISED UK<br>HAEMATOPATHOLOGY DIAGNOSTIC SERVICE<br>S. Barrans, Leeds (UK)</td></tr><tr><td>10:15</td><td>096</td><td>GENOME WIDE-ANALYSIS OF T(14;18)-NEGATIVE FOLLICULAR LYMPHOMA<br>L. Quintanilla-Martinez de Fend, Tübingen (Germany)</td></tr><tr><td>09:00-12:00<br>Auditorium<br>(USI Università)</td><td></td><td>WORKSHOP – CONTEMPORARY LYMPHOMA TREATMENT: RADIATION THERAPY ISSUES<br>Organized in collaboration with the International Lymphoma Radiation Oncology Group - ILROG<br>open to all 15-ICML attendees<br>Part 1: FRACTIONATION ISSUES IN RADIOTHERAPY OF LYMPHOMAS<br>Chair: M.K. Gospodarowicz, Toronto, ON (Canada)</td></tr><tr><td>09:00</td><td></td><td>DOSE PER FRACTION, RESPONSE, LATE EFFECTS RELATIONSHIP IN LYMPHOMAS<br>R. Hoppe, Stanford, CA (USA)</td></tr><tr><td>09:20</td><td></td><td>OPTIMAL DOSE FRACTIONATION FOR INDOLENT AND AGGRESSIVE LYMPHOMAS<br>P. Hoskin, London and Manchester (UK)</td></tr><tr><td>09:40</td><td></td><td>OPTIMAL DOSE FRACTIONATION IN HODGKIN LYMPHOMAS<br>C. Baues, Cologne (Germany)</td></tr><tr><td>10:00-10:25</td><td></td><td>COFFEE BREAK inside Auditorium (USI Università), for attendees</td></tr><tr><td>10:25</td><td></td><td>Part 2: RADIOTHERAPY IN THE ELDERLY LYMPHOMA PATIENT<br>LYMPHOMA IN THE ELDERLY - SCOPE OF THE PROBLEMS<br>I. Glimelius, Uppsala (Sweden)</td></tr><tr><td>10:45</td><td></td><td>RADIOTHERAPY &amp; LYMPHOMA IN THE ELDERLY: INDOLENT LYMPHOMAS<br>U. Ricardi, Turin (Italy)</td></tr><tr><td>11:00</td><td></td><td>RADIOTHERAPY &amp; LYMPHOMA IN THE ELDERLY: AGGRESSIVE LYMPHOMA<br>J. Yahalom, New York, NY (USA)</td></tr><tr><td>11:15</td><td></td><td>RADIOTHERAPY &amp; LYMPHOMA IN THE ELDERLY: HODGKIN LYMPHOMA<br>L. Specht, Copenhagen (Denmark)</td></tr><tr><td>11:30</td><td></td><td>RADIOTHERAPY &amp; LYMPHOMA IN THE ELDERLY: LATE EFFECTS<br>D. Hodgson, Toronto, ON (Canada)</td></tr><tr><td>11:45</td><td></td><td>QUESTIONS</td></tr><tr><td>10:30-11:00<br>Marquee, Cinema Corso<br>and USI Università</td><td></td><td>COFFEE BREAK</td></tr></table>
<table><thead><tr><th></th><th></th><th></th></tr></thead><tbody><tr><td>11:00-12:00<br>Room A, B, Marquee,<br>Cinema Corso and Aula<br>Magna (USI Università)</td><td></td><td><strong>SESSION 7 - HODGKIN LYMPHOMA</strong><br>Co-chairs: R.H. Advani, Stanford, CA (USA) and T.A. Lister, London (UK)</td></tr><tr><td>11:00</td><td>097</td><td>STAGE I-II NODULAR LYMPHOCYTE-PREDOMINANT HODGKIN LYMPHOMA IN THE MODERN ERA: A MULTI-INSTITUTIONAL EXPERIENCE OF ADULT PATIENTS BY ILROG<br>M.S. Binkley, Stanford, CA (USA)</td></tr><tr><td>11:15</td><td>098</td><td>NIVOLUMAB PLUS DOXORUBICIN, VINBLASTINE AND DACARBAZINE FOR NEWLY DIAGNOSED ADVANCED-STAGE CLASSICAL HODGKIN LYMPHOMA: CHECKMATE 205 COHORT D 2-YEAR FOLLOW-UP<br>S. Ansell, Rochester, MN (USA)</td></tr><tr><td>11:30</td><td>099</td><td>CONSOLIDATION RADIOTHERAPY COULD BE OMITTED IN ADVANCED HODGKIN LYMPHOMA WITH LARGE NODAL MASS IN COMPLETE METABOLIC RESPONSE AFTER ABVD. FINAL ANALYSIS OF THE RANDOMIZED HD0607 TRIAL<br>A. Gallamini, Nice (France)</td></tr><tr><td>11:45</td><td>100</td><td>COST-EFFECTIVENESS AND COST-UTILITY ANALYSIS OF MULTIPLE TREATMENT STRATEGIES USING ABVD AND/OR BEACOPP IN THE TREATMENT OF ADVANCED-STAGE HODGKIN LYMPHOMA<br>A. Prica, Toronto, ON (Canada)</td></tr><tr><td>12:00-13:00<br>Marquee</td><td></td><td><strong>LUNCH TIME AND POSTER VIEWING</strong><br>from 12:30 to 13:00 authors in front of their poster for discussion with attendees</td></tr><tr><td>13:00-13:45<br>Room A, B, Marquee,<br>Cinema Corso and Aula<br>Magna (USI Università)</td><td></td><td><strong>JOHN ULTMANN MEMORIAL LECTURE</strong><br>sponsored by the European School of Oncology-ESO<br>Laudatio: J.M. Vose, Omaha, NE (USA)</td></tr><tr><td>13:45-15:00</td><td>003</td><td>THIRTY YEARS OF T-CELL LYMPHOMAS<br>P. Gaulard, Créteil (France)</td></tr><tr><td>Room A<br>and Cinema Corso</td><td></td><td>4 parallel sessions</td></tr><tr><td>13:45</td><td>101</td><td><strong>SESSION 8 - FOLLICULAR LYMPHOMA</strong><br>Co-chairs: B.S. Kahl, St. Louis, MO (USA) and M. Herold, Erfurt (Germany)<br>PROGNOSTIC IMPLICATIONS OF THE MICROENVIRONMENT IN FOLLICULAR LYMPHOMA UNDER RITUXIMAB AND RITUXIMAB+LENALIDOMIDE THERAPY; A TRANSLATIONAL STUDY OF THE SAKK35/10 TRIAL<br>S. Dirnhofer, Basel (Switzerland)</td></tr><tr><td>14:00</td><td>102</td><td>DECIPHERING THE CONTRIBUTION OF MACROPHAGES TO FOLLICULAR LYMPHOMA PATHOGENESIS: NEW INSIGHTS INTO THERAPY<br>P. Perez Galan, Barcelona (Spain)</td></tr><tr><td>14:15</td><td>103</td><td>IMPACT OF PET IMAGING AND HISTOLOGIC TRANSFORMATION ON THE PROGNOSIS OF EARLY DISEASE PROGRESSION IN FOLLICULAR LYMPHOMA<br>C.L. Batlevi, New York, NY (USA)</td></tr><tr><td>14:30</td><td>104</td><td>RESPONSE ORIENTED MAINTENANCE THERAPY IN ADVANCED FOLLICULAR LYMPHOMA. RESULTS OF THE INTERIM ANALYSIS OF THE FOLL12 TRIAL CONDUCTED BY THE FONDAZIONE ITALIANA LINFOMI<br>M. Federico, Modena (Italy)</td></tr><tr><td>14:45</td><td>105</td><td>INTERIM UPDATE FROM A PHASE 2 MULTICENTER STUDY OF TAZEMETOSTAT, AN EZH2 INHIBITOR, IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA<br>F. Morschhauser, Lille (France)</td></tr><tr><td>Room B<br>and Marquee</td><td></td><td><strong>SESSION 9 - EXTRANODAL LYMPHOMAS</strong><br>Co-chairs: M.K. Gospodarowicz, Toronto, ON (Canada) and E. Zucca, Bellinzona (Switzerland)</td></tr><tr><td>13:45</td><td>106</td><td>INTEGRATIVE GENOMIC ANALYSIS IDENTIFIES KEY PATHOGENIC CONCEPTS IN PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA<br>A. Mottok, Ulm (Germany)</td></tr></tbody></table>
<table><tr><td>14:00</td><td>107</td><td>OUTCOME OF PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA IN THE RITUXIMAB ERA: IMPACT OF A PET-GUIDED APPROACH<br/>A. Hayden, Vancouver, B.C. (Canada)</td></tr><tr><td>14:15</td><td>108</td><td>NIVOLUMAB COMBINED WITH BRENTUXIMAB VEDOTIN FOR RELAPSED/REFRACTORY PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA: EFFICACY AND SAFETY FROM THE PHASE 2 CHECKMATE 436 STUDY<br/>P.L. Zinzani, Bologna (Italy)</td></tr><tr><td>14:30</td><td>109</td><td>R-CHOP PRECEDED BY ENGINEERED TUMOR NECROSIS FACTOR (TNF) IN RELAPSED OR REFRACTORY PRIMARY DIFFUSE LARGE B-CELL LYMPHOMA OF THE CNS (rPCNSL): FINAL RESULTS OF THE INGRID TRIAL<br/>A.J. Ferreri, Milan (Italy)</td></tr><tr><td>14:45</td><td>110</td><td>POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD) AFTER SOLID ORGAN TRANSPLANT (SOT): SURVIVAL AND PROGNOSTICATION AMONG 570 PATIENTS (PTS) TREATED IN THE MODERN ERA<br/>D. Jagadeesh, Cleveland, OH (USA)</td></tr><tr><td>14:15-17:30<br/>Auditorium<br/>(USI Università)</td><td></td><td>IBSA FOUNDATION SPECIAL FORUM - REVOLUTIONARY THERAPIES FOR CANCER<br/>Chairmen: F. Cavalli, Bellinzona (Switzerland) and A. Alimonti, Bellinzona (Switzerland)<br/>Organized by IBSA Foundation for Scientific Research<br/>Open to all 15-ICML attendees, appreciated pre-registration at www.ibsafoundation.org (free session)</td></tr><tr><td>14:15</td><td></td><td>WELCOME AND INTRODUCTION<br/>S. Misiti, IBSA Foundation and A. Alimonti, IBSA Foundation Scientific Board</td></tr><tr><td>14:30</td><td></td><td>mTOR SIGNALING IN GROWTH AND METABOLISM<br/>M. Hall, Basel (Switzerland)</td></tr><tr><td>15:00</td><td></td><td>INNATE IMMUNITY, INFLAMMATION AND CANCER: FROM BENCH TO BEDSIDE<br/>A. Mantovani, Milan (Italy), London (UK)</td></tr><tr><td>15:30</td><td></td><td>BUILDING NEXT GENERATION CAR T CELLS<br/>C.H. June, Philadelphia, PA (USA)</td></tr><tr><td>16:00</td><td></td><td>FROM MOLECULAR ADDICTION TO IMMUNE ACTIVATION: REINVENTING THERAPIES FOR CANCER<br/>S. Peters, Lausanne (Switzerland)</td></tr><tr><td>14:15-17:15<br/>Aula Magna<br/>(USI Università)</td><td></td><td>UCLI-ICML JOINT SESSION-NEW DATA ON T-CELL AND OTHER LYMPHOMAS<br/>Honorary Presidents: F. Cavalli, Bellinzona (Switzerland) and J. Ma, Harbin (China)<br/>Executive Presidents: W.J. Chng, Singapore (Singapore), J. M. Vose, Omaha, NE (USA),<br/>J. Zhu, Beijing (China)</td></tr><tr><td>14:20</td><td>111</td><td>20-YEAR SURVIVAL DATA ANALYSIS OF PTCL PATIENTS IN PEKING UNIVERSITY CANCER HOSPITAL<br/>Y. Song, Beijing (China)</td></tr><tr><td>14:45</td><td>112</td><td>DEVELOPING IMMUNOEPIGENETIC PLATFORMS FOR PTCL: LEVERAGING A LOGIC FOR PD1/PDL-1 INHIBITORS<br/>O.A. O'Connor, New York, NY (USA)</td></tr><tr><td>15:10</td><td>113</td><td>CLINICAL OUTCOME OF AN PROSPECTIVE, MULTICENTRE, RANDOMIZED, PHASE III NON-INFERIORITY CLINICAL TRIAL FOR PATIENTS WITH EXTRANODAL NK/T CELL LYMPHOMA TREATED BY P-GEMOX OR ASPAMETDEX<br/>H. Huang, Guangzhou (China)</td></tr><tr><td>15:35-15:55</td><td></td><td>COFFEE BREAK inside Aula Magna (USI Università), for attendees</td></tr><tr><td>15:55</td><td>114</td><td>NEW DATA IN THE MOLECULAR PATHOLOGY OF T CELL LYMPHOMAS<br/>L. de Leval, Lausanne (Switzerland)</td></tr><tr><td>16:20</td><td>115</td><td>DIFFUSE LARGE B-CELL LYMPHOMA: USING IMMUNE BIOMARKERS TO DEFINE NOVEL THERAPIES<br/>W. Zhao, Shanghai (China)</td></tr><tr><td>16:45</td><td>116</td><td>THE RELEVANCE OF OBSERVATIONAL REGISTRIES: THE CASE OF T CELL LYMPHOMA PROJECTS 1.0 AND 2.0<br/>M. Federico, Modena (Italy)</td></tr></table>
<table><tbody><tr><td>15:00-15:30<br>Marquee</td><td></td><td><strong>COFFEE BREAK</strong></td></tr><tr><td>15:30-15:45<br>Room A, B, Marquee<br>and Cinema Corso</td><td></td><td><strong>REPORT OF THE 15-ICML WORKSHOP</strong><br>Co-chairs: S.S. Neelapu, Houston, TX (USA) and G. Salles, Lyon (France)<br>BRIDGING LIQUID BIOPSY INTO MANAGEMENT OF LYMPHOMA PATIENTS: DEVELOPMENT OF FRAMEWORKS FOR CLINICAL RESEARCH AND RECOMMENDATIONS FOR CLINICAL PRACTICE<br>W.H. Wilson, Bethesda, MD (USA)</td></tr><tr><td>15:45-17:15<br>Room A, B, Marquee<br>and Cinema Corso</td><td></td><td><strong>SESSION 10 - ADVANCES IN CAR T-CELL TREATMENT</strong><br>Co-chairs: S.S. Neelapu, Houston, TX (USA) and G. Salles, Lyon (France)</td></tr><tr><td>15:45</td><td>117</td><td>NOVEL BAFF-R CAR T-CELL THERAPY FOR CD19 ANTIGEN-LOSS RELAPSED B CELL TUMORS<br>L.W. Kwak, Duarte, CA (USA)</td></tr><tr><td>16:00</td><td>118</td><td>PHASE I CLINICAL TRIAL OF CD19-TARGETED 19-28Z/4-1BBL "ARMORED" CAR T CELLS IN PATIENTS WITH RELAPSED OR REFRACTORY NHL AND CLL INCLUDING RICHTER TRANSFORMATION<br>C.L. Batlevi, New York, NY (USA)</td></tr><tr><td>16:15</td><td>119</td><td>CD30-CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS FOR THERAPY OF HODGKIN LYMPHOMA (HL)<br>C.A. Ramos, Houston, TX (USA)</td></tr><tr><td>16:30</td><td>120</td><td>DURABLE RESPONSES AFTER CD19-TARGETED CAR-T CELL IMMUNOTHERAPY WITH CONCURRENT IBRTINIB FOR CLL AFTER PRIOR IBRTINIB FAILURE<br>J. Gauthier, Seattle, WA (USA)</td></tr><tr><td>16:45</td><td>121</td><td>HIGH RATE OF DURABLE COMPLETE REMISSION IN FOLLICULAR LYMPHOMA AFTER CD19 CAR-T CELL IMMUNOTHERAPY<br>A.V. Hirayama, Seattle, WA (USA)</td></tr><tr><td>17:00</td><td>122</td><td>SAFETY OF LISOCABTAGENE MARALEUCEL GIVEN WITH DURVALUMAB IN PATIENTS WITH RELAPSED/REFRACTORY AGGRESSIVE B-CELL NON HODGKIN LYMPHOMA: FIRST RESULTS FROM THE PLATFORM STUDY<br>T. Siddiqi, Duarte, CA (USA)</td></tr><tr><td>17:15-17:35<br>Room A, B, Marquee<br>and Cinema Corso</td><td></td><td><strong>SPECIAL LECTURE</strong><br>Chair: F. Cavalli, Bellinzona (Switzerland)</td></tr><tr><td></td><td>123</td><td>THE HIGH COST OF CANCER DRUGS: WHAT CAN WE DO?<br>S.V. Rajkumar, Rochester, MN (USA)</td></tr><tr><td>17:35-18:30<br>Marquee</td><td></td><td><strong>FAREWELL APERO</strong></td></tr></tbody></table>

## Saturday, June 22, 2019

<table><tbody><tr><td>08:30-10:30<br>Auditorium<br>(USI Università)</td><td><strong>ESO-ESMIT Educational Session - PET-CT IN LYMPHOMA</strong><br>Chair: A.T. Lister, London (UK)<br>Organized by the European School of Oncology-ESO and the European School of Multimodality Imaging & Therapy-ESMIT<br><strong>Open to all 15-ICML attendees</strong></td></tr><tr><td>08:30</td><td>HOW TO INTERPRET PET-CT SCANS IN LYMPHOMAS: VISUAL AND FUNCTIONAL EVALUATION<br>M. Meignan, Creteil (France)</td></tr><tr><td>08:50</td><td>PET-BASED CLINICAL DECISIONS: WHERE DO WE STAND AND WHERE WE MAY GO<br>P.W.M. Johnson, Southampton (UK)</td></tr><tr><td>09:20</td><td>THE LUGANO CLASSIFICATION 5 YEARS AFTER: SHOULD WE CHANGE ANYTHING?<br>B.D. Cheson, Washington, D.C. (USA)</td></tr><tr><td>09:40</td><td>CHALLENGING CASES FROM THE ONCOLOGY INSTITUTE OF SOUTHERN SWITZERLAND<br>Presented by E. Zucca, Bellinzona (Switzerland) and L. Ceriani, Bellinzona (Switzerland)<br>Discussants: A.T. Lister, London (UK) and all faculty</td></tr></tbody></table>
<table><tr><td>08:30-10:00</td><td colspan="2">SESSION 11 - NEW DRUG COMBINATIONS</td></tr><tr><td>Room A and B</td><td colspan="2">Co-chairs: A. Younes, New York, NY (USA) and M. Dreyling, Munich (Germany)</td></tr><tr><td>08:30</td><td>124</td><td>PRIMARY ANALYSIS RESULTS OF THE SINGLE-ARM PHASE II STUDY OF MOR208 PLUS LENALIDOMIDE IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (L-MIND)<br/>G. Salles, Lyon (France)</td></tr><tr><td>08:45</td><td>125</td><td>BET INHIBITOR RG6146, VENETOCLAX, AND RITUXIMAB IS A HIGHLY ACTIVE REGIMEN IN RELAPSED/REFRACTORY (R/R) DLBCL: INITIAL REPORT OF PHASE 1B SAFETY, BIOMARKER, AND RESPONSE DATA<br/>M. Dickinson, Melbourne (Australia)</td></tr><tr><td>09:00</td><td>126</td><td>POLATUZUMAB VEDOTIN (POLA) + OBINUTUZUMAB (G) + LENALIDOMIDE (LEN) IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL): PHASE IB/II INTERIM ANALYSIS<br/>A. McMillan, Nottingham (UK)</td></tr><tr><td>09:15</td><td>127</td><td>THE PI3K&Delta; INHIBITOR ME-401 &plusmn; RITUXIMAB IN RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL), CHRONIC LYMPHOCYTIC LEUKEMIA (CLL), AND SMALL LYMPHOCYTIC LYMPHOMA (SLL)<br/>A.D. Zelenetz, New York, NY (USA)</td></tr><tr><td>09:30</td><td>128</td><td>INVESTIGATING SAFETY AND PRELIMINARY EFFICACY OF AFM13 PLUS PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY HODGKIN LYMPHOMA AFTER BRENTUXIMAB VEDOTIN FAILURE<br/>S.M. Ansell, Rochester, MN (USA)</td></tr><tr><td>09:45</td><td>129</td><td>TARGETING THE PERIPHERAL T-CELL LYMPHOMA (PTCL) EPIGENOME WITH ORAL 5-AZACYTIDINE AND ROMIDEPSIN: RESULTS AND CLINICAL-MOLECULAR CORRELATIONS FROM A PHASE 2 STUDY<br/>L. Falchi, New York, NY (USA)</td></tr><tr><td>10:15-11:15</td><td colspan="2">"FOCUS ON" SESSION - INDOLENT NON-FOLLICULAR LYMPHOMA</td></tr><tr><td>Room A and B</td><td colspan="2">Chair: G.S. Nowakowski, Rochester, MN (USA)</td></tr><tr><td>10:15</td><td>130</td><td>EARLY PROGRESSION OF DISEASE (POD24) PREDICTS SHORTER SURVIVAL IN MALT LYMPHOMA PATIENTS RECEIVING SYSTEMIC TREATMENT<br/>A. Conconi, Ponderano (Italy)</td></tr><tr><td>10:25</td><td>131</td><td>INTRALESIONAL RITUXIMAB SUPPLEMENTED WITH AUTOLOGOUS SERUM IN RELAPSED CD20+ INDOLENT LYMPHOMAS OF THE CONJUNCTIVA: ACTIVITY AND SAFETY RESULTS OF THE "IRIS" TRIAL<br/>A.J. Ferreri, Milan (Italy)</td></tr><tr><td>10:35</td><td>132</td><td>MULTI-OMICS LANDSCAPE OF SPLENIC MARGINAL ZONE LYMPHOMA (SMZL) - INTERIM ANALYSIS OF IELSG46 STUDY<br/>A. Bruscaggin, Bellinzona (Switzerland)</td></tr><tr><td>10:45</td><td>133</td><td>UMBRALISIB MONOTHERAPY DEMONSTRATES EFFICACY AND SAFETY IN PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA: A MULTICENTER, OPEN-LABEL, REGISTRATION DIRECTED PHASE 2 STUDY<br/>P.L. Zinzani, Bologna (Italy)</td></tr><tr><td>10:55</td><td>134</td><td>IBRUTINIB FOR THE TREATMENT OF BING-NEEL SYNDROME: A RETROSPECTIVE, MULTICENTER STUDY<br/>J. Castillo, Boston, MA (USA)</td></tr><tr><td>11:05</td><td>135</td><td>IBRUTINIB MONOTHERAPY PRODUCES LONG-TERM DISEASE CONTROL IN PREVIOUSLY TREATED WALDENSTROM'S MACROGLOBULINEMIA: FINAL REPORT OF THE PIVOTAL TRIAL (NCT01614821)<br/>S.P. Treon, Boston, MA (USA)</td></tr><tr><td>11:15-11:40</td><td colspan="2">15-ICML HIGHLIGHTS</td></tr><tr><td>Room A and B</td><td colspan="2">"TAKE HOME MESSAGES"<br/>J.W. Friedberg, Rochester, NY (USA)</td></tr></table>

(Continues)
11:40-11:50
CLOSURE AND FAREWELL
F. Cavalli, Bellinzona (Switzerland)

13:30-18:00
IV INTERNATIONAL WORKSHOP ON CANINE LYMPHOMA - HOW TO STAGE CANINE LYMPHOMA IN 2019
Room B

Co-chairs: L. Aresu, Turin (Italy), S. Comazzi, Milan (Italy), F. Guscetti, Zurich (Switzerland) and L. Marconato, Bologna (Italy)

Organized by the European Canine Lymphoma Network

open to all 15-ICML attendees

This icon denotes presentations that will be audio- and video-recorded and available online, only for 15-ICML attendees, starting from July 2019, thanks to an unrestricted grant.
SATELLITE SYMPOSIUM PROGRAM AND AGENDA
(as of May 15, 2019)

Tuesday, June 18, 2019

<table><tbody><tr><td>13:30-15:00</td><td>2 parallel symposia</td></tr><tr><td>Room B I</td><td><strong>KITE, A GILEAD COMPANY</strong><br/><strong>CAR T: FROM BED TO BENCH AND BACK AGAIN</strong><br/>Chair: C. Roddie, London (UK)<br/>The journey of CAR T therapy from apheresis to processing and back for infusion is complex with many considerations including logistics and GMP-compliance requirements. Furthermore, there are challenges associated with scalability including the ability to increase manufacturing capacity without compromising quality. This symposium will discuss many of the key considerations associated with manufacturing CAR T therapies and explore potential methods to overcome them including automation. This will help ensure successful and timely delivery of CAR T to as many patients as possible. Use of non-conforming or out of specification products in the clinic will also be discussed.<br/><br/><strong>INTRODUCTION</strong><br/>C. Roddie, London (UK)<br/><br/><strong>OVERVIEW OF DEVELOPMENT JOURNEY: FROM BENCH TO BEDSIDE</strong><br/>J. Rossi (United States)<br/><br/><strong>FROM PATIENT TO COMMERCIAL PRODUCTION: APHERESIS TO SAMPLE SHIPPING</strong><br/>C. Roddie, London (UK)<br/><br/><strong>FROM SAMPLE RECEIPT TO CAR T PRODUCT</strong><br/>C. Shen and L. van de Wiel (The Netherlands)<br/><br/><strong>PRODUCT RELEASE TESTS: HELPING ENSURE PATIENT SAFETY AND GUARANTEEING QUALITY</strong><br/>C. Chabannon, Marseilles (France)<br/><br/><strong>SCALING CAR T FOR A GMP STANDARD PRODUCT</strong><br/>C. Roddie, London (UK)</td></tr><tr><td>Room B II</td><td><strong>PFIZER ONCOLOGY</strong><br/><strong>RITUXIMAB BIOSIMILAR: AN OPPORTUNITY TO FOSTER INNOVATION IN LYMPHOMA TREATMENT</strong><br/>Chair: J. Sharman, Eugene, OR (USA)<br/>Rituximab based therapies is in many instances the standard-of-care approach for patients with FL, DLBCL and CLL. In some patients Chemo-free Rituximab combination therapy may be the most appropriate. However, the increase cost of biologics could potentially be a limiting factor to improve patient's outcomes world-wide. The utilization of Rituximab Biosimilar may offer the opportunity to upgrade patient access to expensive treatments. In addition, given the landscape of the Biosimilars field, rigorous and well-designed RWE Biosimilar studies are critical to address data gaps and obtain coverage upon evidence generation. The adoption of Rituximab Biosimilar may help to meet high medical needs while maintaining affordability.</td></tr><tr><td>13:30</td><td>WELCOME AND INTRODUCTION<br/>J. Sharman, Eugene, OR (USA)</td></tr><tr><td>13:40</td><td>BIOSIMILAR: "DO BIOSIMILARS HAVE SIMILAR SAFETY PROFILE AND EFFICACY"? CURRENT PERSPECTIVE<br/>J. Goncalves, Lisboa (Portugal)</td></tr><tr><td>14:00</td><td>REAL WORD EVIDENCE IN BIOSIMILARS. DECISION MAKING IN THE REAL-WORLD<br/>A. Mato, New York, NY (USA)</td></tr><tr><td>14:20</td><td>RITUXIMAB BIOSIMILAR IN FOLLICULAR LYMPHOMA. EARLY USE OF RITUXIMAB<br/>J. Sharman, Eugene, OR (USA)</td></tr><tr><td>14:40</td><td>PANEL DISCUSSION<br/>All</td></tr><tr><td>16:00-17:30</td><td>3 parallel symposia</td></tr></tbody></table>

(Continues)
<table><thead><tr><th></th><th></th></tr></thead><tbody><tr><td>Room A</td><td>NOVARTIS ONCOLOGY<br>MAXIMIZING CLINICAL BENEFIT IN LYMPHOMAS: EXPLORING THE UTILITY OF CAR-T CELL THERAPY<br>Chair: U. Jäger, Vienna (Austria)<br>In the satellite symposium "Maximizing Clinical Benefit in Lymphomas: Exploring the Utility of CAR-T Cell Therapy," Dr. Ulrich Jäger (chair) and additional faculty will lead an interactive discussion regarding the role of CAR-T cell therapy in lymphomas. Key themes addressed will include defining the diffuse large B-cell lymphoma continuum of care and best practices for adverse event management; in addition, the potential future utility of CAR-T cell therapy in non-Hodgkin lymphoma -including combination partners, use in earlier lines of therapy, and role for pediatric patients - will be covered.</td></tr><tr><td>16:00-16:05</td><td>INTRODUCTIONS AND OPENING REMARKS<br>U. Jäger, Vienna (Austria)</td></tr><tr><td>16:05-16:25</td><td>DEFINING THE UTILITY OF CAR-T CELL THERAPY IN THE DLBCL CONTINUUM OF CARE<br>U. Jäger, Vienna (Austria)</td></tr><tr><td>16:25-16:45</td><td>EXPLORING ADDITIONAL ROLES FOR CAR-T CELL THERAPY IN NHL<br>A. Sureda, Barcelona (Spain)</td></tr><tr><td>16:45-17:00</td><td>RATIONALE AND FUTURE DIRECTIONS FOR CAR-T CELL THERAPY IN PEDIATRIC NHL<br>K. Curran, New York, NY (USA)</td></tr><tr><td>17:00-17:15</td><td>PRACTICAL CONSIDERATIONS FOR TOXICITY MANAGEMENT WITH CAR-T CELL THERAPY<br>S. Schuster, Philadelphia, PA (USA)</td></tr><tr><td>17:15-17:25</td><td>PANEL DISCUSSION AND Q&A<br>All</td></tr><tr><td>17:25-17:30</td><td>CLOSING REMARKS<br>U. Jäger, Vienna (Austria)</td></tr><tr><td>Room B I</td><td>BRISTOL-MYERS SQUIBB<br>RATIONALE: RESEARCH AND NEW THERAPEUTIC APPROACHES-I-O NOVEL AGENTS ADVANCING LYMPHOMA EXPECTATIONS<br>Chair: P.L. Zinzani, Bologna (Italy)<br>This symposium, sponsored by Bristol-Myers Squibb, describes recent advances in treating patients with lymphoma using immuno-oncology (I-O) agents and the utilization of biomarkers to further understand the underlying disease biology and inform novel targeting strategies. Following an introduction to I-O clinical trial advances and ongoing investigations, there will be a discussion of recent key data in salvage and maintenance settings and their potential impact on post-transplant treatment. The final presentation will focus on the potential of biomarkers in lymphoma to inform future clinical trials. A question-and-answer session will provide an opportunity for the participants to interact with the faculty experts.</td></tr><tr><td>16:00-16:05</td><td>WELCOME AND INTRODUCTIONS<br>P.L. Zinzani, Bologna (Italy)</td></tr><tr><td>16:05-16:25</td><td>ONGOING IMMUNO-ONCOLOGY EXPLORATIONS IN LYMPHOMA<br>P.L. Zinzani, Bologna (Italy)</td></tr><tr><td>16:25-16:45</td><td>OPTIMIZING PERI-TRANSPLANT THERAPY WITH IMMUNO-ONCOLOGY<br>A. Herrera, Duarte, CA (USA)</td></tr><tr><td>16:45-17:05</td><td>BIOMARKER DISCOVERY IN LYMPHOMA<br>B. Chapuy, Göttingen (Germany)</td></tr><tr><td>17:05-17:25</td><td>OPEN DISCUSSION WITH THE EXPERTS<br>All</td></tr><tr><td>17:25-17:30</td><td>CLOSING REMARKS<br>P.L. Zinzani, Bologna (Italy)</td></tr><tr><td>Room B II</td><td>KITE, A GILEAD COMPANY<br>CAR T THERAPY: A CLOSER LOOK AT THE SCIENCE BEHIND THE CELLS<br>Chair: M. Topp, Würzburg (Germany)<br>The science surrounding CAR T response and safety profiles is still emerging. During this highly interactive symposium, factors involved in these outcomes including biomarkers of response to treatment as well as the potential underlying mechanisms for common toxicities will be discussed. This symposium will also look at future developments and see how outcomes for patients may be improved with CAR T technologies including third generation-, dual antigen specific-CARs and TRUCKs. We encourage you to take the opportunity to ask our experts questions and learn more about the scientific advancements for these novel therapies for patients treated with CAR T.<br>INTRODUCTION AND OVERVIEW<br>M. Topp, Würzburg (Germany)</td></tr></tbody></table>
INTEGRATING KEY TRANSLATIONAL FINDINGS WITH PATIENT OUTCOMES

C. Bonini, Milan (Italy)

UNDERSTANDING FACTORS LEADING TO NON-RESPONSES

M. Topp, Würzburg (Germany)

Q&A AND PANEL DISCUSSION

All

THE FUTURE OF CAR T THERAPY

K. Peggs, London (UK)

Q&A AND PANEL DISCUSSION

All

18:30-20:00 4 parallel symposia

Room A

ROCHE

ANTIBODY THERAPIES FOR PATIENTS WITH DLBCL: WHAT DOES THE FUTURE HOLD?

Chair: L.H. Sehn, Vancouver B.C. (Canada)

While many patients with diffuse large B-cell lymphoma (DLBCL) can be cured with current front-line therapy, a significant proportion relapse or are refractory to treatment. High-dose chemotherapy and stem-cell transplantation are possible for some of these patients, but many are ineligible due to co-morbidities or disease refractory to chemotherapy; these patients face a dismal outcome. An international faculty of experts will discuss treatment and management of both front-line and relapsed/refractory DLBCL, with a focus on novel antibody therapies. Join us to examine how the DLBCL landscape may evolve in the near future as new data and treatment options become available.

18:30-18:35 INTRODUCTION
L.H. Sehn, Vancouver B.C. (Canada)

18:35-18:45 WHAT OPTIONS DO OUR PATIENTS HAVE FOR FIRST-LINE TREATMENT?
A. Lopez Guillermo, Barcelona (Spain)

18:45-18:55 WHAT'S NEXT FOR PATIENTS WHO RELAPSE OR ARE REFRACTORY TO TREATMENT?
M.J. Matasar, New York, NY (USA)

18:55-19:10 CAN NOVEL ANTIBODY THERAPIES IMPROVE OUTCOMES FOR PATIENTS WITH R/R DLBCL?
F. Morschhauser, Lille (France)

19:10-19:25 POLATUZUMAB VEDOTIN: CLINICAL DATA IN R/R DLBCL
L.H. Sehn, Vancouver B.C. (Canada)

19:25-19:40 WHAT MIGHT THE FUTURE HOLD FOR DLBCL TREATMENT STRATEGIES?
A. McMillan, Nottingham (UK)

19:40-19:55 PANEL DISCUSSION
All

19:55-20:00 CLOSING REMARKS
L.H. Sehn, Vancouver B.C. (Canada)

Room B I

BAYER

PRECISION MEDICINE IN MALIGNANT LYMPHOMA: IS IT A REALITY?

Chair: M. Ghielmini, Bellinzona (Switzerland)

Precision medicine has traditionally been a personalized approach to the treatment of solid tumors with the advent of biomarker-driven strategies. However, when it comes to the treatment of malignant lymphoma, is precision medicine a reality? Join the esteemed faculty Dr. Michele Ghielmini, Dr. Margaret Shipp, Dr. Louis Staudt, and Professor Martin Dreyling in their invigorating exploration of genetic heterogeneity in aggressive lymphoma, clinical exploration of precision medicine in DLBCL, and enrichment strategies in indolent lymphoma with the aim of uncovering whether precision medicine is a reality in malignant lymphoma.

WELCOME AND OPENING REMARKS

M. Ghielmini, Bellinzona (Switzerland)

GENETIC HETEROGENEITY IN AGGRESSIVE LYMPHOMA AND POTENTIAL THERAPEUTIC IMPLICATIONS

M.A. Shipp, Boston, MA (USA)

CLINICAL EXPLORATION OF PRECISION MEDICINE IN DLBCL

L.M. Staudt, Bethesda, MD (USA)

PATIENT ENRICHMENT STRATEGIES AND THERAPY SELECTION IN MALIGNANT LYMPHOMAS

M. Dreyling, Munich (Germany)

PANEL DISCUSSION/Q&A

Chair: M. Ghielmini, Bellinzona (Switzerland)
## Room B II
### TAKEDA ONCOLOGY ON THE FRONTLINE: MANAGING PATIENTS WITH CD30+ HL AND PTCL

Chair: M. Hutchings, Copenhagen (Denmark)

This satellite symposium supported by Takeda Oncology aims to highlight the current treatment landscape and recent developments in frontline CD30+ HL and PTCL. The latest data from studies in frontline CD30+ HL and PTCL will be discussed, as well as challenges and management strategies for patients in these settings. This symposium will be highly interactive with opportunities for the audience to tailor the topic of discussion during each presentation. There will also be a dedicated question and answer session to enable open interaction between the participants and the faculty.

18:30-18:35 WELCOME AND INTRODUCTION
M. Hutchings, Copenhagen (Denmark)

18:35-18:55 TAILOR-THE-TOPIC: HL DISCUSSIONS
M. Hutchings, Copenhagen (Denmark)

18:55-19:15 THE LATEST RESULTS IN THE MANAGEMENT OF FRONTLINE CD30+ HL
J.M. Connors, Vancouver BC (Canada)

19:15-19:35 CURRENT LANDSCAPE AND RECENT DEVELOPMENTS IN THE FRONTLINE MANAGEMENT OF CD30+ PTCL
S.M. Horwitz, New York, NY (USA)

19:35-19:55 PANEL Q&A
Faculty, facilitated by M. Hutchings, Copenhagen (Denmark)

19:55-20:00 SUMMARY AND CLOSE
M. Hutchings, Copenhagen (Denmark)

## Auditorium, USI Università
### LYMPHOMA HUB NEW CHEMOTHERAPY-FREE APPROACHES FOR THE TREATMENT OF LYMPHOID MALIGNANCES

Chair and co-chair: G. Salles, Lyon (France) and A. Younes, New York, NY (USA)

This symposium brings together an international panel of experts who will discuss the novel chemotherapy-free treatment approaches for lymphoid malignancies. Presentations will focus on diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic lymphoma, navigating the rapidly evolving treatment landscapes. The new chemotherapy-free treatment options will be explored alongside the current standards of care. Each presentation will be followed by a question and answer session to allow for discussion with the expert panel. Come and join the debate on whether it is possible to switch to the chemotherapy-free agents.

For more information visit: https://icml.lymphomahub.com/en

18:30-18:35 OBJECTIVES AND INTRODUCTIONS
G. Salles, Lyon (France)

18:35-18:45 DLBCL-CHEMOTHERAPY-FREE REGIMENS: PROS AND CONS
U. Jäger, Vienna (Austria)

18:45-18:55 ROUND TABLE ON DLBCL
All

18:55-19:05 FL-CHEMOTHERAPY-FREE REGIMENS: PROS AND CONS
N.H. Fowler, Houston, TX (USA)

19:05-19:15 ROUND TABLE ON FL
All

19:15-19:25 MCL-CHEMOTHERAPY-FREE REGIMENS: PROS AND CONS
S. Rule, Plymouth (UK)

19:25-19:35 ROUND TABLE ON MCL
All

19:35-19:45 CLL-CHEMOTHERAPY-FREE REGIMENS: PROS AND CONS
M. Hallek, Cologne (Germany)

19:45-19:55 ROUND TABLE ON CLL
All

19:55-20:00 MEETING CONCLUSION
A. Younes, New York, NY (USA)
Wednesday, June 19, 2019

<table><tr><td>18:30-20:00</td><td>3 parallel symposia</td></tr><tr><td>Room A</td><td>JANSSEN PHARMACEUTICAL COMPANIES OF JOHNSON &amp; JOHNSON<br>CHALLENGING THE STANDARDS OF CARE IN THE MANAGEMENT IN B-CELL LYMPHOMAS<br>Co-chairs: C. Buske, Ulm (Germany) and S. Rule, Plymouth (UK)<br>Therapeutic advances in lymphoma have been made over many decades. A deeper understanding of disease pathogenesis guided the development of targeted therapies for patients with MCL and WM. Consequently, providing tolerable and curative therapies to many lymphoma patients is now possible. However, some specific challenges still remain, including limited investigations into rare lymphoma subtypes and using backbone chemotherapy regimens for initial therapy. Our faculty will discuss studies challenging current standards of care and the potential to improve patient outcomes in various B-cell lymphomas.</td></tr><tr><td>18:30-18:40</td><td>WELCOME AND INTRODUCTION<br>C. Buske, Ulm (Germany)</td></tr><tr><td>18:40-19:00</td><td>HOW ARE TARGETED THERAPIES IMPACTING THE MANAGEMENT OF PATIENTS WITH MANTLE CELL LYMPHOMA (MCL)?<br>S. Rule, Plymouth (UK)</td></tr><tr><td>19:00-19:20</td><td>CAN WE IMPROVE ON R-CHOP FOR PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA (DLBCL)?<br>G. Lenz, Münster (Germany)</td></tr><tr><td>19:20-19:40</td><td>DOES CHEMOTHERAPY STILL HAVE A ROLE IN WALDENSTRÖM'S MACROGLOBULINEMIA (WM)?<br>S.P. Treon, Boston, MA (USA)</td></tr><tr><td>19:40-20:00</td><td>PANEL DISCUSSION AND CLOSING REMARKS<br>C. Buske, Ulm (Germany) and all</td></tr><tr><td>Room B</td><td>MEDSCAPE EDUCATION<br>CHALLENGING CURRENT PARADIGMS IN CLL: TIME AND TREATMENT<br>Supported by an independent educational grant from AbbVie<br>Chair: P. Hillmen, Leeds (UK)<br>The concept of time-limited therapy is not new; chemotherapy regimens are of fixed duration. However, recent years have seen the emergence of therapies, such as Bruton tyrosine kinase (BTK) inhibitors, which require continuous treatment. In contrast, B-cell lymphoma 2 (Bcl-2)-inhibitor combinations have been developed as 2-year and 1-year fixed-duration therapies, offering new time-limited treatment options. Furthermore, both approaches are- or will potentially be-approved in both front-line and relapse settings, challenging both initial treatment selection and sequencing decisions.<br>This symposium explores the current and emerging treatment paths for patients with treatment-naive chronic lymphocytic leukemia (CLL) and the impact of initial choices on treatment options in relapse.</td></tr><tr><td>18:30-18:40</td><td>WELCOME AND INTRODUCTION<br>P. Hillmen, Leeds (United Kingdom)</td></tr><tr><td>18:40-19:00</td><td>NOVEL CONCEPTS IN CLL PRACTICE<br>P. Hillmen, Leeds (United Kingdom)</td></tr><tr><td>19:00-19:20</td><td>CURRENT AND EMERGING PARADIGMS: TIME-LIMITED THERAPY<br>B. Eichhorst, Cologne (Germany)</td></tr><tr><td>19:20-19:40</td><td>CURRENT AND EMERGING PARADIGMS: CHRONIC THERAPY<br>M. Davids, Boston, MA (USA)</td></tr><tr><td>19:40-20:00</td><td>CHALLENGES IN PRACTICE: INITIAL TREATMENT SELECTION AND SEQUENCING THERAPY<br>Panel and Audience Debate</td></tr><tr><td>Auditorium,<br>USI Università</td><td>SANDOZ ONCOLOGY<br>VARIABILITY OF BIOLOGICS AND ITS IMPACT ON BIOSIMILAR DEVELOPMENT<br>Chair: P. Cornes, Bristol (UK)<br>Biologics are highly complex to manufacture and their immunogenicity, tolerability, and efficacy profiles can be affected by significant manufacturing process changes. As such, manufacturing changes must be carefully monitored at every step, in order to ensure the correct product identity throughout the lifecycle.<br>Biosimilars are developed using highly sensitive analytical methods and tailored clinical programs. The advent of biosimilars allowed for a much more detailed analysis of batch-to-batch variability and manufacturing shifts of reference medicines. Recently, some shifts in quality attributes of reference medicines have been reported by biosimilar manufacturers.<br>The faculty will discuss the potential impact of biologic variability on clinical outcomes and biosimilar development.<br>(References available on request)</td></tr><tr><td>18:30-18:45</td><td>THE REGULATORY PERSPECTIVE<br>H. Schellekens, Utrecht (The Netherlands)</td></tr></table>
<table><tr><td>18:45-19:00</td><td>THE ANALYTICAL PERSPECTIVE<br/>M. Schiestl, Kundl (Austria)</td></tr><tr><td>19:00-19:15</td><td>THE CLINICIAN'S PERSPECTIVE<br/>W. Jurczak, Krakow (Poland)</td></tr><tr><td>19:15-19:30</td><td>THE PATIENT PERSPECTIVE<br/>P. Cornes, Bristol (UK)</td></tr><tr><td>19:30-20:00</td><td>DEBATE AND Q&A<br/>All faculty</td></tr></table>

Thursday, June 20, 2019

<table><tr><td>18:30-20:00</td><td>2 parallel symposia</td></tr><tr><td>Room A</td><td><strong>CELGENE</strong><br/><strong>INDIVIDUALIZING TREATMENT AND EMERGING THERAPIES IN B-CELL MALIGNANCIES</strong><br/>Chair: U. Vitolo, Turin (Italy)<br/>Recent clinical developments are transforming the treatment of indolent and aggressive B-cell malignancies. Chemotherapy-free therapies are altering the therapeutic landscape of both frontline and relapsed/refractory follicular lymphoma. Additionally, frontline treatment of diffuse large B-cell lymphoma is becoming increasingly individualized with a focus on selecting optimal therapies according to cell of origin. Meanwhile, the emergence of CAR T therapies for the treatment of various non-Hodgkin lymphomas and chronic lymphocytic leukemias have the potential to shift treatment paradigms entirely. Key emerging data in B-cell malignancies will be highlighted and discussed by experts in the field.</td></tr><tr><td>18:30-18:35</td><td>WELCOME AND INTRODUCTIONS<br/>U. Vitolo, Turin (Italy)</td></tr><tr><td>18:35-18:55</td><td>TREATMENT IN THE CHEMOTHERAPY-FREE ERA IN FRONT-LINE AND RELAPSED AND REFRACTORY FOLLICULAR LYMPHOMA<br/>J.P. Leonard, New York, NY (USA)</td></tr><tr><td>18:55-19:15</td><td>OPTIMIZING FRONTLINE DLBCL TREATMENT: THE ROLE OF CELL OF ORIGIN<br/>U. Vitolo, Turin (Italy)</td></tr><tr><td>19:15-19:35</td><td>EMERGING ROLE OF CAR T THERAPIES IN THE TREATMENT OF NHL AND CLL<br/>D.G. Maloney, Seattle, WA (USA)</td></tr><tr><td>19:35-20:00</td><td>CLOSING AND Q&A<br/>U. Vitolo, Turin (Italy) and All</td></tr><tr><td>Room B</td><td><strong>MORPHOSYS</strong><br/><strong>SURVIVAL, SAFETY, SIMPLICITY: TRANSFORMING TREATMENT SEQUENCING IN DLBCL</strong><br/>Co-chairs: B.D. Cheson, Washington DC (USA) and G. Salles, Lyon (France)<br/>Join us for this interactive symposium as we explore DLBCL treatment approaches: the progress made, remaining challenges, and the potential future of the treatment landscape. With an emphasis on the patient journey, we will seek to understand the issues faced beyond the first-line treatment setting, and hear expert insights to navigate real-world treatment decision-making challenges. In addition, through advances in DLBCL disease understanding, we will provide perspectives on how novel treatment approaches may be utilized to achieve new treatment strategies for patients who experience relapsed or refractory DLBCL.</td></tr><tr><td>18:30-18:35</td><td>WELCOME AND INTRODUCTION<br/>Co-chairs: B.D. Cheson, Washington DC (USA) and G. Salles, Lyon (France)</td></tr><tr><td>18:35-18:45</td><td>DLBCL TREATMENT LANDSCAPE: CURRENT PERSPECTIVE<br/>G.S. Nowakowski, Rochester, MN (USA)</td></tr><tr><td>18:45-19:00</td><td>THE PATIENT JOURNEY: TREATMENT DECISION MAKING IN REAL-WORLD PRACTICE<br/>J.R. Westin, Houston, TX (USA)</td></tr><tr><td>19:00-19:10</td><td>PANEL DISCUSSION<br/>All</td></tr><tr><td>19:10-19:25</td><td>THE FUTURE FOR DLBCL: TRANSFORMING OUR APPROACHES AND TREATMENT SEQUENCING?<br/>A. Davies, Southampton (UK)</td></tr><tr><td>19:25-19:40</td><td>TARGETING CD19: A NOVEL ANTIBODY STRATEGY<br/>G. Salles, Lyon (France)</td></tr></table>
19:40-19:55 PANEL DISCUSSION
All

19:55-20:00 SUMMARY AND CLOSE
B.D. Cheson, Washington DC (USA)

Friday, June 21, 2019

Room A ONCOLOGY INSTITUTE OF SOUTHERN SWITZERLAND-IOSI

18:30-19:30 "THE BIG DEBATE: POINT COUNTER POINT"
ARE NEW EXPENSIVE ANTI-LYMPHOMA DRUGS WORTH THE MONEY?

Chair: M. Ghielmini, Bellinzona (Switzerland)

Supported by Gilead Sciences who provided funding.

Often targeted therapy, immunotherapy and CAR-T cells are registered at high price for indications for which they have at most demonstrated an increase in PFS and not in OS. The Big Debate, organized by the Oncology Institute of Southern Switzerland (IOSI) has become a tradition, and this year will discuss this issue. In three short debates, 6 distinguished speakers (10 minutes each) will argue, for three different classes of drugs, if the results of new and expensive treatment do or not justify their very high costs.

BCR PATHWAY INHIBITORS

Yes: M. Dreyling, Munich (Germany) vs No: A. Davies, Southampton (UK)

IMID'S

Yes: S. Rule, Plymouth (UK) vs No: G. Salles, Lyon (France)

CART-T CELLS

Yes: A. Sureda, Barcelona (Spain) vs No: L.H. Sehn, Vancouver B.C. (Canada)
# ORAL PRESENTATIONS

## KEYNOTE LECTURES

### 001
NEXT GENERATION CAR T CELLS FOR LYMPHOMA AND BEYOND

C.H. June

Perelman School of Medicine, University of Pennsylvania, Center for Cellular Immunotherapies, Philadelphia, PA, United States

Engineered T cells that encode transgenic T cell receptors (TCR) or chimeric antigen receptors (CAR) are increasingly being tested as a new modality for cancer immunotherapy. In this presentation we will review emerging patterns of efficacy and toxicity after adoptive cell transfer (ACT), with a focus on blood cancers. Striking efficacy has been observed in acute and chronic B cell leukemia and lymphoma. More unexpectedly, strong antitumor effects are being observed in multiple trials in patients with advanced refractory and relapsed myeloma. In some cases, toxicity has been predicted in preclinical models. In other cases, toxicity was only uncovered after results from Phase 1 clinical trial results were in hand. Onset of toxicity can be immediately observed following infusion of cells or maybe delayed. Toxicity usually occurs coincident with peak (Cmax) levels of adoptively transferred cells. Today with more than 1,000 patients having been infused with genetically engineered human T cells, genotoxicity has not been reported. To date, the induction of irAE appears to be less than with checkpoint therapies, although more experience with ACT is required to determine the ultimate incidence of autoimmune toxicities.

**Keywords:** T-cell receptor (TCR).

**Disclosures:** June, C: Research Funding: Parker Institute for Cancer Immunotherapy, NIH/NCI, Tmunity Therapeutics.

### 002
PRECISION EPIGENETIC THERAPY FOR B-CELL LYMPHOMA

A. Melnick

Medicine, Weill Cornell Medical College, New York City, United States

Mutation in epigenetic modifier genes is one of the hallmarks of lymphomas such as DLBCL and FL. Invariable the genes mutated play critical roles in the B-cells during the germinal center response and their

mutation results in aberrant retention of germinal center features. Somatic mutations of EZH2 result in enzymatic gain of function leading to aberrant silencing of bivalent promoters affecting genes involved in B-cell terminal differentiation and cell cycle checkpoints. CREBBP and EP300 are tumor suppressors in B-cell lymphomas. Loss of function of these genes drives lymphomagenesis through aberrant silencing of gene enhancers linked to antigen presentation and germinal center exit programs. Notably mutations in CREBBP and EZH2 result in loss of immune surveillance due to epigenetic silencing of MHC class II and MHC class I proteins. Loss of function mutations of the histone methyltransferase KMT2D disrupts enhancer monomethylation of H3K4, resulting in attenuated response to extracellular signals derived from T-cells such as CD40. Loss of function mutations of TET2 occur in ~10% of patients with DLBCL and drive transformation of B-cells due to reduction of enhancer DNA hydroxymethylation, which results in their loss of function. The principle biological effect of TET2 loss of function in the cell of origin is to block differentiation, which results in their eventual malignant transformation. We have identified specific epigenetic therapies that antagonize the effects of each of these mutations and can be used as precision therapy for these patients as well as adjuvants to immunotherapies by restoring the ability of T-cells to recognize lymphoma cells.

**Keywords:** B-cell lymphoma; diffuse large B-cell lymphoma (DLBCL); EZH2.

**Disclosures:** Melnick, A: Employment Leadership Position: Janssen Biotech; Consultant Advisory Role: Consultant; Stock Ownership: None; Honoraria: N/A; Research Funding: Yes, Research Support.

### 003
THIRTY YEARS OF T-CELL LYMPHOMAS

P. Gaulard

Pathology, Hôpital Henri Mondor, Creteil, France

Peripheral T-cell lymphomas (PTCLs) are characterized by a usually aggressive clinical course. Owing to their rarity and diversity, most PTCLs remain a diagnostic issue and a therapeutic challenge. However, these last 30 years have been a major break in the field of PTCL. From morphologically based classification, the first PTCL entities started to be recognized in the 1980s. Since then, the concept that malignant lymphomas relate to a cell of origin together with the recognition of new recurrent genetic alterations led to the delineation of
around 30 distinct clinicopathological PTCL entities in the current WHO classification.

Follicular helper T cells (TFH) appear as the cell counterpart of a major proportion of PTCL worldwide, including angio-immunoblastic T-cell lymphoma and other nodal lymphomas with a TFH phenotype; the later disclose a rather homogeneous mutational landscape which recapitulates a multi-step oncogenic process associating epigenetic deregulation (TET2 +/- DNMT3A mutations, often at early stages), and second hit mutations affecting the T-cell receptor signaling pathway (RHOA,...). This oncogenic model has been confirmed in mouse models and opens the field for using emerging epigenetic- or signaling-modulating therapies. Among anaplastic large cell lymphoma (ALCL), those with ALK rearrangement constitute the best-delineated entity. ALK-negative ALCLs appear genetically heterogeneous with translocation-associated subsets (DUSP22, TP63,...) found in both systemic and cutaneous types. DUSP22-rearranged ALK-negative ALCL likely constitutes a unique category with a distinct signature and a good outcome. Except for DUSP22-rearranged ALCL, a constitutive activation of STAT3 is shared by ALK-positive and ALK-negative ALCLs, including the newly described usually indolent breast implant-associated ALCL. Lymphomas derived from cells of the innate immune system affect preferentially extranodal sites, which are continuously exposed to various antigens. Chronic immunosuppression and genetic background may also play a role. There is evidence of plasticity in terms of cellular derivation (NK, Tγδ, Tαβ) within a single entity. Most of these tumors also harbor a combination of mutations affecting different classes of epigenetic modifyers, and mutation-induced activation of the JAK-STAT pathway which may serve as potential therapeutic targets. While most of these proliferations are highly malignant, some more indolent forms have been identified, arising in the skin or the GI tract. Despite significant progress in the understanding of PTCLs, 20-30% of PTCL patients remain "unspecified", a basket category which may contain emerging (GATA3 or T-bet) subtypes.

Most PTCL probably harbor distinct therapeutic vulnerabilities supporting the need for biologically-oriented therapeutic strategies to improve patient's outcome.

**Keywords:** peripheral T-cell lymphomas (PTCL).

**Disclosures:** GAULARD, P: Consultant Advisory Role: Takeda; Honoraria: Takeda, Roche; Research Funding: Takeda, Celgene, Innate Pharma.

PLENARY SESSION

004
IDENTIFYING MUTATIONS ENRICHED IN RELAPSED-REFRACTORY DLBCL TO DERIVE GENETIC FACTORS UNDERLYING TREATMENT RESISTANCE

C. Rushton¹ | M. Alcaide¹ | M. Cheung¹ |
N. Thomas¹ | S. Arthur¹ | N. Michaud² | S. Daigle² |
J. Davidson¹ | K. Bushell¹ | S. Yu¹ | M. Jain³ |
L. Shepherd⁴ | M. Crump³ | K. Mann⁵ |
J. Kuruvilla³ | S. Assouline⁶ | N. Johnson⁵ |
D.W. Scott⁷ | R.D. Morin¹

¹Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada; ²Epizyme, Cambridge, United States; ³Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada; ⁴Canada Cancer Trials Group, Queen's University, Kingston, Canada; ⁵Department of Medicine, McGill University, Montreal, Canada; ⁶Department of Oncology, McGill University, Montreal, Canada; ⁷Genome Sciences Centre, BC Cancer, Vancouver, Canada

**Introduction:** Diffuse Large B-cell Lymphoma (DLBCL) the most common subtype of Non-Hodgkin Lymphoma and is characterized by genetic and clinical heterogeneity. In relapsed/refractory DLBCL (rrDLBCL) cases, where frontline treatment is unsuccessful, patient prognosis is extremely poor, with 2-year overall survival of 20-40%. While numerous treatments are under investigation to improve patient outcomes, their success has been limited as the genetic mechanisms underpinning treatment resistance are largely unknown. Identifying genomic alterations associated with relapse may open new treatment avenues and allow the stratification of patients into subgroups based upon relevant mutations.

**Methods:** We have collected samples from 134 patients enrolled in three clinical trials (LY17, Obinituzumab-GDP, QCROC2) exploring candidate treatment options for rrDLBCL. For each patient enrolled, blood plasma samples were collected prior to and at several time points following candidate treatment. A combination of exome sequencing and target panel sequencing of lymphoma-associated genes was performed on cell-free DNA extracted from plasma samples and tissue biopsies (where available) obtained upon trial enrollment (relapse). Somatic mutations were identified using Strelka2, and clonal population structure was inferred using PyClone. Mutation prevalence was compared to a large unselected cohort of diagnostic DLBCLs to identify genes enriched for mutations.

**Results:** Patients with rrDLBCL were enriched for mutations in 5 genes; TP53 (Q=6.74x10⁻⁵), IL4R (Q=0.00391), HVCN1 (Q=0.0729), RB1 (Q=0.0127) and MS4A1 (Q=0.0522), with TP53 mutations previously associated with rrDLBCL. Mutations in IL4R may lead to constitutively active JAK/STAT signalling and inferior overall survival in DLBCL. HVCN1 encodes a voltage-gated proton channel which modulates the B-Cell Receptor (BCR), and truncated HVCN1 isoforms have been shown to enhance BCR signaling. MS4A1 encodes CD20, the target of the monoclonal antibody Rituximab, a cornerstone of frontline DLBCL treatment. In several patients, clonal subpopulations with MS4A1 mutations underwent clonal selection following treatment. These mutations are predicted to either truncate CD20, or destabilize a common transmembrane helix, with 4/15 patients containing mutations affecting Tyrosine 86. We also observed recurrent in-frame
deletions targeting S1680 of CREBBP, and although CREBBP muta-
tions are associated with treatment resistance in other cancers, the
functional effect of this deletion has not been characterized.

**Conclusions:** DLBCL patients with mutations in relapse-enriched genes are at a higher risk of treatment failure. Mutations in these genes, specifically hotspot deletions, may have power as biomarkers to identify patients at a high risk of relapse and could inform on the mechanism of acquired resistance to components of R-CHOP.

**Keywords:** CD20; diffuse large B-cell lymphoma (DLBCL); R-CHOP.

**Disclosures:** Michaud, N: Employment Leadership Position: Epizyme.

Daigle, S: Employment Leadership Position: Epizyme.

005

ROBUST: First report of phase III randomized
study of lenalidomide/R-CHOP (R²-CHOP) vs
placebo/R-CHOP in previously untreated
ABC-type diffuse large B-cell lymphoma

U. Vitolo<fnref n="1" /> | T.E. Witzig² | R.D. Gascoyne³ |

D.W. Scott³ | Q. Zhang⁴ | W. Jurczak⁵ |

M. Özcan⁶ | X. Hong⁷ | J. Zhu⁸ | J. Jin⁹ |

D. Belada¹⁰ | J.M. Bergua¹¹ | F. Piazza¹² |

H. Mócikova¹³ | A.L. Molinari¹⁴ | D.H. Yoon¹⁵ |

F. Cavallo¹⁶ | M. Tani¹⁷ | K. Izutsu¹⁸ | K. Kato¹⁹ |

M. Czuczman²⁰ | S. Hersey²⁰ | A. Kilcoyne²⁰ |

J. Russo²⁰ | K. Hudak²⁰ | J. Zhang²⁰ |

A. Chiappella<fnref n="1" /> | G.S. Nowakowski² | on behalf of the
ROBUST study investigators

First Affiliated Hospital of Medical School of Zhejiang University, First Hospital of Zhejiang Province, Zhejiang, Hangzhou, China; ¹⁰Fourth Department of Internal Medicine-Hematology, Charles University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic; ¹¹Servicio de Hematología, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain; ¹²Division of Hematology, Department of Medicine, University of Padova and Azienda Ospedaliera di Padova, Padova, Italy; ¹³Department of Internal Medicine and Haematology, Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic; ¹⁴UO Ematologia, Ospedale Degli Infermi, Rimini, Italy; ¹⁵Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Republic of Korea; ¹⁶AOU Città della Salute e della Scienza di Torino, Turin, Italy; ¹⁷U.O. Ematologia, Dipartimento Oncologia e Ematologia, Ospedale Santa Maria delle Croci, Ravenna, Italy; ¹⁸National Cancer Center Hospital, Tokyo, Japan; ¹⁹Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka City, Japan; ²⁰Clinical Research & Development, Celgene Corporation, Summit, NJ, USA

**Introduction:** The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) continues to convey inferior survival despite efforts to enhance outcomes with novel R-CHOP combinations. Phase II studies have suggested that the addition of the immunomodulatory agent lenalidomide to R-CHOP could ameliorate the poor prognostic effect of the ABC phenotype and improve treatment outcome in this subgroup of patients.

**Methods:** The global phase III ROBUST trial (NCT02285062) is the first to compare lenalidomide/R-CHOP (R²-CHOP) vs placebo/R-CHOP in previously untreated, prospectively selected, CD20+ ABC-type DLBCL. Patients included adults with Ann Arbor stage II-IV disease, IPI score ≥ 2, and ECOG PS ≤ 2. Confirmation of histology and cell-of-origin type were prospectively analyzed from formalin-fixed, paraffin-embedded excisional/surgical or core needle biopsy samples by central pathology using the NanoString Lymphoma Subtyping Test (LST), based on the Lymph2Cx GEP assay (Scott, Blood 2014). ABC-DLBCL patients were stratified by IPI score (2 vs ≥ 3), bulky disease (< 7 vs ≥ 7 cm) and age (< 65 vs ≥ 65 y), and randomized 1:1 to

<figure><img src="image_2.png" /></figure>

<footnote n="1">¹Division of Hematology, A.O.U. Città della Salute e della Scienza Hospital and University, Torino, Italy; ²Division of Hematology, Mayo Clinic, Rochester, MN, United States; ³Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada; ⁴Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China; ⁵Department of Hematology, Jagiellonian University, Krakow, Poland; ⁶Department of Hematology, Ankara University, Ankara, Turkey; ⁷Cancer Hospital, Fudan University, Shanghai, China; ⁸Beijing Cancer Hospital, Beijing, China; ⁹The</footnote>
lenalidomide PO 15 mg/d, d1-14/21 + standard R-CHOP21 vs placebo/R-CHOP21 for 6 cycles, with 2 additional, optional doses of rituximab per local practice. The primary endpoint was progression-free survival (PFS) assessed by independent central radiology per 2014 NHL IWG criteria, and defined as time from randomization to PD or death from any cause.

**Results:** A total of 570 ABC-DLBCL patients met eligibility criteria and were enrolled in ROBUST (n = 285 per arm). Baseline demographics were similar between arms, with a median age for all patients of 65 y (52% ≥ 65 y), 42% IPI 2 score/58% IPI ≥ 3 score, 88% stage III/IV disease, and 34% bulky disease. The primary endpoint of PFS was not met with an HR = 0.85 (95% CI, 0.63-1.14) and P = 0.29; median PFS was not reached for either arm (Figure). Positive PFS trends favoring R²-CHOP over placebo/R-CHOP were observed with disease stage III/IV (HR = 0.81 [95% CI, 0.60-1.10]) and IPI score ≥ 3 (HR = 0.74 [95% CI, 0.53-1.05]). Median EFS was not reached for either arm (HR = 1.04; 95% CI, 0.80-1.34; P = 0.73). At a median follow-up of 27.1 mo (range, 0-47) for survivors, 2-y OS was 79% for R²-CHOP and 80% for placebo/R-CHOP (medians not reached). ORR was 91% for both arms, with 69% vs 65% CR for R²-CHOP vs placebo/R-CHOP, respectively. 74% R²-CHOP and 84% placebo/R-CHOP patients completed 6 cycles of treatment; AEs (mainly neutropenia) were the most common reason for treatment discontinuation. The most common grade 3/4 AEs (≥ 10%) for R²-CHOP vs placebo/R-CHOP were neutropenia (60% vs 48%), anemia (22% vs 14%), thrombocytopenia (17% vs 11%), leukopenia (14% vs 15%), febrile neutropenia (14% vs 9%), and lymphopenia (11% vs 8%).

**Conclusions:** Overall, the ROBUST study did not meet the primary endpoint of PFS for R²-CHOP vs placebo/R-CHOP in previously untreated patients with ABC-DLBCL, although a positive trend favoring R²-CHOP has been observed in advanced stage and higher risk patients. The safety profile of R²-CHOP was consistent with those of individual medicines, and no new safety signals were identified with the combination.

## 006
### ADDITION OF LENALIDOMIDE TO R-CHOP (R2CHOP) IMPROVES OUTCOMES IN NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): FIRST REPORT OF ECOG-ACRIN1412 A RANDOMIZED PHASE 2 US INTERGROUP STUDY OF R2CHOP VS R-CHOP

G.S. Nowakowski¹ | F. Hong² | D.W. Scott³ |

R. Macon⁴ | R.L. King⁴ | T.M. Habermann¹ |

N. Wagner-Johnston⁵ | C. Casulo⁶ | J.L. Wade⁷ |

G.G. Nagargoje⁸ | C.M. Reynolds⁹ | J.B. Cohen¹⁰ |

N. Khan¹¹ | J. Amengual¹² | K.L. Richards¹³ |

R.F. Little¹⁴ | J.P. Leonard¹³ | J.W. Friedberg⁶ |

L. Kostakoglu¹⁵ | B.S. Kahl³ | T.E. Witzig¹

¹Division of Hematology, Mayo Clinic, Rochester, MN, USA; ²Department of Biostatistics, Dana Farber Cancer Institute, Boston, MA, USA; ³British Columbia Cancer Center for Lymphoid Cancer, Vancouver, Canada;

⁴Division of Hematopathology, Mayo Clinic Rochester MN, USA; ⁵Johns Hopkins University, Baltimore, Maryland, USA; ⁶University of Rochester, NY, USA; ⁷Heartland NORP, Decatur, IL, USA; ⁸Marcy Hospital, Coon Rapids, MN, USA; ⁹Saint Joseph Mercy Hospital, Ann Arbor, MI, USA;

¹⁰Emory University-Winship Cancer Institute, Atlanta, GA, USA; ¹¹Fox Case Cancer Center, Philadelphia, PA, USA; ¹²Columbia University Medical Center, New York, NY, USA; ¹³Weill Cornell Medicine, New York, NY, USA; ¹⁴National Cancer Institute, Bethesda, MD; ¹⁵Mount Sinai Hospital, New York, NY, USA; ³Department of Hematology, Washington University School of Medicine, St. Louis, MO, USA

**Introduction:** Lenalidomide has single-agent activity in relapsed DLBCL. Single arm phase I/II trials of lenalidomide with RCHOP (R2CHOP) for untreated DLBCL have shown the regimen to be safe with promising activity, particularly in the activated B-cell-like (ABC) subtype. ECOG-ACRIN trial 1412 (E1412) is a randomized phase II study comparing R2CHOP vs R-CHOP in previously untreated DLBCL.

**Methods:** Eligible patients were ≥ 18 years, with pathologically confirmed DLBCL regardless of COO, stage II bulky-IV disease, IPI ≥ 2, ECOG PS ≤ 2 and measurable disease. Patients were randomized 1:1 and stratified by International Prognostic Index (2/3 vs 4/5) and age (<60 vs ≥ 60 y) to lenalidomide PO 25 mg/d, d1-10 q21d + standard RCHOP21 vs RCHOP21 for 6 cycles. Paraffin-embedded tumor tissue from the initial biopsy were analyzed using the NanoString Lymph2Cx GEP assay allowing for outcome analysis in ABC DLBCL. The primary endpoint was progression-free survival (PFS). With anticipated 289 evaluable patients (102 ABC-DLBCL), the study was designed to have 89% power at one-sided 0.1 significance level with 89 PFS events for testing in all patients, and 81% power at one-sided 0.125 significance level with 40 PFS events in ABC DLBCL. Secondary endpoints included response rate and overall survival (OS). Kaplan Meier method was used to estimate PFS and OS, stratified log-rank test and Cox model were used to compare between arms and estimate hazard ratios (HR).

**Results:** 349 patients were enrolled between 8/2013 to 1/2017; 280 patients (145 R2CHOP, 135 RCHOP) were evaluable (ineligibility was primarily due to central pathology exclusion or lack of diagnostic material for central review); 94 were ABC-DLBCL; 122 GCB-DLBCL and 18 Unclassified. Baseline patient characteristics are balanced between arms, median age 66 (range 24-92); 61% male; 88% white; 70% stage IV; 34%, 43% and 24% IPI 2, 3 and 4/5, respectively. Toxicity was as expected with R-CHOP; significantly different rates of grade ≥3 adverse events between arms were: diarrhea (6% vs. 0.6% of patients, p=0.005), febrile neutropenia (25% vs. 12% of patients, p=0.003), and thrombocytopenia (36% vs. 12% of patients, p<.0001) in R2CHOP vs R-CHOP arm, respectively. 86% and 85% patients completed 6 cycles of therapy in R2CHOP and RCHOP arms respectively. The overall and complete response rates were 92% and 67% in R-CHOP and 97% (p=0.12) and 72% (p=0.44) in R2-CHOP arm, respectively. With a median follow-up was 2.4 years; R2CHOP was
<figure><img src="image_3.png" /></figure>

associated with a 33% reduction in risk of progression or death vs RCHOP, HR 0.67 (95% CI 0.44-1.03), p (one-sided) =0.03 (Figure). The 2-year overall survival was 87% and 80%, respectively. Based on COO, PFS HR for R2CHOP was: 0.68 for ABC, p=0.15, 0.86 for GCB, 0.83 for Unclassified and 0.61 for unknown cases.

**Conclusion:** The addition of lenalidomide to R-CHOP (R2CHOP) in this phase II study improved PFS in newly diagnosed DLBCL.

**Keywords:** diffuse large B-cell lymphoma (DLBCL); gene expression profile (GEP); immunochemotherapy.

**Disclosures:** Nowakowski, G: Celgene consultancy (personally uncompensated) and research support; MorphoSys consultancy (personally uncompensated), research support, Bayer: consultancy (personally uncompensated) and research support, Curis: research support, Roche: Research support, Genentech: Research support, NanoStrings Technologies: research support. Scott, DW: Named inventor on a patent licensed to NanoString Technologies [Institution], Research funding: Janssen, Roche/Genentech, NanoString Technologies, Consulting: Janssen, Travel: Celgene. Macon, R: Celgene research support. Leonard, JP: Consulting: Sutro, Bayer, Gilead, AstraZeneca, Celgene, Merck, Morphosys, Beigene, Nordic Nanovector, Roche/Genentech, ADC Therapeutics, Sandoz, Karyopharm, Miltenyi, Akcea Therapeutics. Kostakoglu, L: Roche/Gentech: Research support. Kahl, BS: Consulting: Celgene, Genentech, Roche, AbbVie, Pharmacyclics, Astra Zeneca. Witzig, TE: Research support: Celgene, Spectrum, Acerta, Consulting (personally uncompensated): Incyte, Seattle Genetics, Abbvie, Morphosys, Spectrum, Celgene. Consulting personally compensated: Immune Design, Karyopharm.

## 007
# IBRUTINIB VERSUS PLACEBO IN PATIENTS WITH ASYMPTOMATIC, TREATMENT-NAÏVE EARLY STAGE CLL: PRIMARY ENDPOINT RESULTS OF THE PHASE 3 DOUBLE-BLIND RANDOMIZED CLL12 TRIAL

P. Langerbeins¹ | J. Bahlo¹ | C. Rhein¹ |

H. Gerwin¹ | P. Cramer¹ | M. Fürstenau¹ |

O. Al-Sawaf¹ | J. von Tresckow¹ | A.M. Fink¹ |

K. Kreuzer¹ | U. Vehling-Kaiser² | E. Tausch³ |

L. Müller⁴ | M. Eckart⁵ | R. Schlag⁶ | W. Freier⁷ |

T. Gaska⁸ | C. Balser⁹ | M. Reiser¹⁰ | M. Stauch¹¹ |

C. Wendtner¹² | K. Fischer¹ | S. Stilgenbauer¹³ |

B. Eichhorst¹ | M. Hallek¹

¹Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University Hospital, Cologne, Germany; ²Hämatologie und Onkologie, Tagesklinik, Landshut, Germany; ³Internal Medicine III, University Hospital, Ulm, Germany; ⁴Hämatologie und Onkologie, Studienzentrum UnterEms, Leer, Germany; ⁵Hämatologie und Onkologie, Onkologische Schwerpunktpraxis, Erlangen, Germany; ⁶Hämatologie und Onkologie, Gemeinschaftspraxis, Würzburg, Germany; ⁷Hämatologie und Onkologie, Medicinum, Hildesheim, Germany; ⁸Klinik für Hämatologie und Onkologie, Brüderkrankenhaus St. Josef, Paderborn, Germany; ⁹Hämatologie und Onkologie, Internistische Praxis, Marburg, Germany; ¹⁰PIOH, Praxis Internistischer Onkologie und Hämatologie, Köln, Germany; ¹¹Hämatologie, Onkologie, Gerinnung, Ambulantes Zentrum, Kronach, Germany; ¹²Department I of Internal Medicine, Munich Clinic Schwabing, Academic Teaching Hospital of University of Munich, Munich, Germany; ¹³Internal Medicine I, University of Saarland, Homburg, Germany

**Introduction:** So far, treatment of asymptomatic, early stage CLL patients has not been proven beneficial. Ibrutinib is a BTK inhibitor with impressive clinical efficacy in advanced or relapsed CLL. Therefore we wished to evaluate whether ibrutinib prolongs event-free survival (EFS) in early stage CLL patients with increased risk of progression.

**Methods:** Asymptomatic Binet A patients were stratified according to a recently developed score (Pflug et al., Blood 2014). Patients with intermediate, high and very high risk were randomized 1:1 to receive ibrutinib 420 mg per day or placebo. EFS was defined as time from randomization until occurrence of active disease according to iwCLL guidelines, new CLL treatment or death. Secondary endpoints progression free survival (PFS) and time to next treatment (TTNT) were defined as time from randomization until progression/death (PFS) or until the date of initiation of subsequent treatment for CLL (TTNT). Survival will be analyzed later with 60% (N=28) of the required events being reported. Patients with low risk (N=152) were allocated to an observational arm and were not included in primary endpoint analysis.

**Results:** A total of 182 or 181 patients were assigned to receive ibrutinib or placebo, respectively. At median observation time of 31 months EFS was not reached in the ibrutinib arm and was 47.8 months in the placebo arm (HR 0.25; 95%CI, 0.14 to 0.43; P<0.0001; Figure 1). Similarly PFS was not reached for ibrutinib and 14.8 months with placebo (HR 0.18; 95%CI, 0.12 to 0.27). TTNT was longer in the ibrutinib arm (HR 0.21; 095%CI, 0.11 to 0.39).
<figure><img src="image_4.png" /><figcaption>**TABLE 1** (S)AEs of particular interest: number of patients (percent). [3 patients of the placebo-arm received 1 cycle (28 days) of ibrutinib]</figcaption></figure>

<table><thead><tr><th></th><th>ibrutinib<br>n=185</th><th>placebo<br>n=178</th><th>P-value</th></tr></thead><tbody><tr><td>Any (S)AE of particular interest</td><td>106 (57.3)</td><td>71 (39.9)</td><td>0.001</td></tr><tr><td>Diarrhea</td><td>58 (31.4)</td><td>44 (24.7)</td><td>n.s.</td></tr><tr><td>• CTC 1-2</td><td>56 (30.2)</td><td>39 (21.9)</td><td></td></tr><tr><td>• CTC 3-4</td><td>2 (1.1)</td><td>5 (2.8)</td><td></td></tr><tr><td>Bleeding</td><td>51 (27.6)</td><td>17 (9.6)</td><td>0.000</td></tr><tr><td>• CTC 1-2</td><td>45 (24.3)</td><td>15 (8.4)</td><td></td></tr><tr><td>• CTC 3-4</td><td>6 (3.2)</td><td>2 (1.2)</td><td></td></tr><tr><td>Atrial fibrillation</td><td>33 (17.8)</td><td>13 (7.3)</td><td>0.003</td></tr><tr><td>• CTC 1-2</td><td>21 (11.3)</td><td>10 (5.6)</td><td></td></tr><tr><td>• CTC 3-4</td><td>11 (6.5)</td><td>3 (1.7)</td><td></td></tr><tr><td>Hypertensive disorders</td><td>18 (9.7)</td><td>7 (3.9)</td><td>0.04</td></tr><tr><td>• CTC 1-2</td><td>15 (8.1)</td><td>4 (2.3)</td><td></td></tr><tr><td>• CTC 3-4</td><td>3 (1.6)</td><td>3 (1.7)</td><td></td></tr></tbody></table>

EFS, PFS and TTNT improvement was consistent across all risk groups analyzed, except for very high risk patients due to small numbers (N=8). At cut-off, 6 and 5 deaths were documented in the ibrutinib and placebo arm, respectively. There was no significant difference in non-serious and serious adverse events (SAE) in ibrutinib and placebo treated patients respectively (82.7 vs. 84.3%). SAEs were reported in 34.6 and 34.8% of ibrutinib and placebo treated patients respectively; most common SAEs were infections (11.4 vs. 11.8%), neoplasms (5.9 vs. 10.7%) and cardiac disorders (8.6 vs. 6.7%). AEs of particular interest were mostly of CTC-grade 1-2

and significantly more frequent in ibrutinib treated patients (Table 1).

**Conclusions:** The results of this study allow to conclude that ibrutinib significantly improves EFS, PFS and TTNT in patients with treatment-naïve early stage CLL when compared to placebo. There were no significant differences in adverse events between both study arms.

**Disclosures:** Langerbeins, P: Consultant Advisory Role: Sunesis; Honoraria: Janssen, Abbvie; Research Funding: Janssen. Cramer, P: Consultant Advisory Role: Janssen, Novartis; Honoraria: Roche, Janssen; Research Funding: Roche, Gilead, GlaxoSmithKline/ Novartis, Janssen. Al-Sawaf, O: Honoraria: Roche, Gilead, Abbvie, Janssen; Research Funding: Beigene. von Tresckow, J: Honoraria: Roche, AbbVie, Janssen; Research Funding: Roche, Janssen. Fink, A: Honoraria: Roche; Research Funding: Celgene. Wendtner, C: Consultant Advisory Role: AbbVie, Roche, Genentech, Gilead, Novartis, Janssen; Honoraria: AbbVie, Roche, Genentech, Gilead, Novartis, Janssen; Research Funding: AbbVie, Roche, Genentech, Gilead, Novartis, Janssen. Fischer, K: Other Remuneration: travel grants by Roche. Stilgenbauer, S: Consultant Advisory Role: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La-Roche, Janssen, Novartis; Honoraria: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La-Roche, Janssen, Novartis; Research Funding: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La-Roche, Janssen, Novartis. Eichhorst, B: Consultant Advisory Role: Janssen, Gilead, Roche, Abbvie, Novartis, Celgene; Honoraria: Roche, Novartis, Gilead, Janssen, Abbvie, Celgene; Research Funding: Roche, Janssen, Abbvie, Gilead. Hallek, M: Consultant Advisory Role: Roche Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, Boehringer; Honoraria: Roche Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, Boehringer;
Research Funding: Roche, Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, Abbvie.

## ACR-ICML JOINT SESSION - THE ROLE OF NON-CLINICAL MODELS AS BRIDGES TO EARLY CLINICAL TRIALS

### 008 DESIGNER ORGANOIDS FOR MODELING EPIGENETICS, SIGNALING, AND THERAPIES IN LYMPHOMA

**A. Singh**

*Biomedical Engineering; Mechanical Engineering; Englander Institute for Precision Medicine, Cornell University, Ithaca, United States*

Diffuse Large B cell lymphoma (DLBCL) is the most common lymphoma with significant molecular heterogeneity within morphologically indistinguishable tumors of the lymph node. Two subtypes of DLBCL have remarkably poor clinical outcomes: the recently defined extranodal class of activated B cell-like (ABC)-DLBCL and the epigenetic class of germinal center B cell (GCB)-DLBCL (1, 2). The mechanism through which DLBCLs, and potentially other lymphomas, are resistant to current therapies are unknown but may be linked to the particular spectrum of somatic mutations in these tumors, which are in concert with complex growth signals provided by the malignant lymph node tumor microenvironment (Ly-TME). Many of the hallmark ABC-DLBCL mutations result in constitutive activation of protein components of B cell receptor (BCR) and Toll-like receptor (TLR) pathways in these malignant immune cells. Hence these pathways are emerging as a source of therapeutic targets for the treatment of ABC-DLBCLs. However, to date, existing BCR pathway inhibitors such as those targeting Bruton's tyrosine kinase are active in a limited subset of patients and only for a short duration, the causes of which are unknown. The substantial differences in response rates and response duration between ABC-DLBCL patients reflect the variable dependencies on BCR and TLR signaling and/or differential regulation by the Ly-TME. Unfortunately, we do not understand the impact of Ly-TME on cooperative, feed-back, and bypass signaling pathways in ABC-DLBCLs and, consequently, on the efficacy of inhibitors and/or agonists to adequately suppress these networks. A major limitation in the field has been the lack of an experimental therapeutics platform that recapitulates human cell and extracellular matrix components of Ly-TME, fluid characteristics and tissue stiffness that regulate DLBCL signaling, and also could model BCR-Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) paracaspase and TLR signaling cross-talk. In this talk, we will discuss the discoveries enabled by designer lymphoid organoids and on-chip technologies in understanding the epigenetic switches such as enhancer of zeste homolog 2 (EZH2) and components of the

B Cell receptor signaling pathway that have emerged as key therapeutic targets in DLBCLs (3-6). We will also discuss the ongoing development of a more accurate 3D on-chip model and test the cooperative signaling between BCR-MALT1-TLR as well as the therapeutic efficacy of select inhibitors alone or in combination with other drugs.

**Research funding:** The authors acknowledge financial support from the National Institutes of Health (1R33CA212968-01 to A.S) and Department of Defense Career Development Award (W81XWH-17-1-0215to A.S.).

**References**

1. B. Chapuy et al., Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. *Nat Med* **24**, 679-690 (2018).

2. J. D. Phelan et al., A multiprotein supercomplex controlling oncogenic signalling in lymphoma. *Nature*, (2018).

3. F. Apoorva et al., How Biophysical Forces Regulate Human B Cell Lymphomas. *Cell Rep* **23**, 499-511 (2018).

4. W. Beguelin et al., EZH2 enables germinal center formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop. *Nature communications* **8**, 877 (2017).

5. A. Purwada et al., ex vivo synthetic immune tissues with T cell signals for differentiating antigen-specific, high affinity germinal center B cells. *Biomaterials* **198**, 27-36 (2019).

6. A. Purwada, A. Singh, Immuno-engineered organoids for regulating the kinetics of B-cell development and antibody production. *Nat Proc* **12**, 168-182 (2017).

**Keywords:** B-cell receptor (BCR); EZH2; Mucosa-Associated Lymphoid Tissue (MALT).

### 009 MOUSE PDX AS NON-CLINICAL MODELS FOR LYMPHOMA

**A. Louissaint**

*Pathology, Harvard Medical School, Boston, MA, United States*

Lymphomas represent nearly 70 distinct diseases with unique clinical presentations, therapeutic responses and underlying biology. There is a pressing shortage of publicly available cell line and in vivo models of nearly all of these diseases, which has severely hampered efforts to understand and target their biology. Most in vivo models of lymphoma are genetically-engineered mouse models, which often don't faithfully recapitulate human disease. To address this issue, we have established a repository of patient-derived xenografts (PDX) of lymphomas by engrafting human tumors into immunodeficient NOD/Scid/IL2rgnnull mice with or without an MHC Class 1 deficiency (to prevent graft versus host disease). Blood and bone marrow specimens involved with tumor were injected by tail vein injection. Lymph node and extranodal biopsy specimens were implanted under the renal capsule as a 1x1x2mm tumor seed, which maintains the *in situ* microarchitecture.
The PDXs have been extensively characterized by immunohistochemistry (IHC), flow cytometry, transcriptome sequencing and targeted DNA sequencing. These studies have demonstrated retention of key architectural, cellular, and molecular features of the primary tumors. Flow cytometric analysis of patient tumors and their respective xenografts revealed highly concordant patterns of surface marker expression. IHC of murine tissues confirmed retention of tumor immunophenotypes, architecture, and even tissue tropism in the PDXs. The genetic characterization of the PDX models using a targeted DNA sequencing approach showed a mutational profile that clearly matched primary lymphoma samples and significantly expands the current repertoire of available pre-clinical models.

These models represent a unique opportunity to interrogate biology and perform preclinical studies with in vivo models. We have utilized models extensively to interrogate chemical, antibody and other therapeutic manipulations. The lymphomas, along with a spectrum of PDXs from other hematologic malignancies, are available through the online portal PRoXe (Public Repository of Xenografts) at http://www.proxe.org.

# 010
ADVANCING OUR UNDERSTANDING AND
TREATMENT OF LYMPHOMA WITH
SPONTANEOUS CANINE MODELS

L. Aresu

Department of Veterinary Science, Grugliasco, Italy

Lymphoma is one of the most frequently diagnosed malignancies in dog and represents the most widely investigated tumor in veterinary medical oncology. Knowledge on the diagnosis, molecular biology, genetics and epigenetics has grown substantially in the recent years. Within the different lymphoma subtypes, canine diffuse large B-cell lymphoma (DLBCL) resembles in many elements the human counterpart, including frequency, molecular abnormalities and similar therapeutic responses to chemotherapy. But, many others aspects are still scarcely known and a complete characterization becomes fundamental when including dogs with DLBCL in clinical trials to test new molecules.

In the NGS era researchers have attempted to fill this gap and to accurately describe canine lymphoma model in a similar fashion to rodent models. This presentation is intended to provide an overview of the main ground-breaking investigations in canine B-cell lymphoma that have been published in the last decade. In three large-scale studies of gene expression profiling, similarities between canine DLBCL and human activated B cell-like DLBCL subtype were found both by DNA-microarray and RNA-seq. NF-kB activation by two pathways, named MyD88-dependent signaling pathway through several Toll-like receptors and Bruton's tyrosine kinase pathway were highlighted in this subtype. Also, functional relevance of

NF-kB activation in dogs with DLBCL was tested using NEMO-binding domain peptide in two clinical trials and the compound resulted safe and blocked NF-kB activity. Few years before treatment with Ibrutinib was found effective in dogs with B-cell lymphoma, however no information about cell of origin was available for these dogs. Interestingly, a peculiar MYC deregulation via the LIN28B/Let-7 axis was identified in canine DLBCL and LIN28B resulted the most upregulated gene both in vivo and in vitro, opening new scenario both for treatment of this tumor in dog and the relevance of this disease as model when testing compounds targeting this pathway.

Moreover, advantages and pitfalls when using dogs with B-cell lymphoma in preclinical experiments for human drug development will be considered in this lecture. To date, drug development pipelines follows common strategy with preclinical testing in cell lines and in mice, PK/PD testing in large animals such as experimental Beagle dogs, and then phase I-III testing in human clinical trials. The inclusion of dogs with lymphomas as part of preclinical testing or in parallel with human trials would be a serious advantage both in data analysis and if results are positive for the expansion to the veterinary market of the new drug. Limitations are also present, including that dogs are from private owners and some toxicities may be species-specific.

In future, we expect an increasing number of clinical trials including data from dogs with DLBCL, but also a detailed pathological and molecular classification of the tumors should be always requested to avoid biases related to the heterogeneity of the disease.

## References:

Aresu L, Ferraresso S, Marconato L, Cascione L, Napoli S, Gaudio E, Kwee I, Tarantelli C, Testa A, Maniaci C, Ciulli A, Hillmann P, Bohnacker T, Wymann MP, Comazzi S, Milan M, Riondato F, Dalla Rovere G, Giantin M, Giannuzzi D, Bertoni F. New molecular and therapeutic insights into canine diffuse large B cell lymphoma elucidates the role of the dog as a model for human disease. Haematologica. 2018 Dec 13. pii: haematol.2018.207027. doi: 10.3324/haematol.2018.207027.

Aresu L. Canine Lymphoma, More Than a Morphological Diagnosis: What We Have Learned about Diffuse Large B-Cell Lymphoma. Front Vet Sci. 2016 Aug 31;3:77. doi: 10.3389/fvets.2016.00077.

Richards KL, Motsinger-Reif AA, Chen HW, Fedoriw Y, Fan C, Nielsen DM, Small GW, Thomas R, Smith C, Dave SS, Perou CM, Breen M, Borst LB, Suter SE. Gene profiling of canine B-cell lymphoma reveals germinal center and postgerminal center subtypes with different survival times, modeling human DLBCL. Cancer Res. 2013 Aug 15;73 (16):5029-39. doi: 10.1158/0008-5472.CAN-12-3546. Epub 2013 Jun 19.

Villarnovo D, McCleary-Wheeler AL, Richards KL. Barking up the right tree: advancing our understanding and treatment of lymphoma with a spontaneous canine model. Curr Opin Hematol. 2017 Jul;24 (4):359-366. doi: 10.1097/MOH.0000000000000357. Review.

**Keywords:** activated B-cell-like (ABC); gene expression profile (GEP); NF-kB.
FOCUS ON... SESSION: MANTLE CELL LYMPHOMA

011

COMBINATION OF IBRUTINIB WITH RITUXIMAB (IR) IS HIGHLY EFFECTIVE IN PREVIOUSLY UNTREATED ELDERLY (>65 YEARS) PATIENTS (PTS) WITH MANTLE CELL LYMPHOMA (MCL) - PHASE II TRIAL

P. Jain<fnref n="1" /> | J. Romaguera<fnref n="1" /> | K. Nomie<fnref n="1" /> | S. Zhang² |

L. Wang² | O. Oriabure<fnref n="1" /> | N. Wagner-Bartak<fnref n="3" /> |

L. Zhang<fnref n="1" /> | F. Hagemeister<fnref n="1" /> | F. Samaniego<fnref n="1" /> |

J. Westin<fnref n="1" /> | H. Ju Lee<fnref n="1" /> | L. Nastoupil<fnref n="1" /> | S. Iyer<fnref n="1" /> |

S. Parmar<fnref n="1" /> | C. Ok<fnref n="1" /> | R. Kanagal-Shamanna<fnref n="1" /> |

W. Chen<fnref n="1" /> | S. Thirumurthi⁴ | D. Santos⁵ |

M. Badillo<fnref n="1" /> | L. Fayad<fnref n="1" /> | S. Neelapu<fnref n="1" /> | N. Fowler<fnref n="1" /> |

M. Wang<fnref n="1" />

¹Lymphoma and Myeloma, UT MD Anderson Cancer Center, Houston, United States; ²Genomic Medicine, UTMDACC, Houston, United States; ³Radiology, UTMDACC, Houston, United States; ⁴Gastroenterology, UTMDACC, Houston, United States; ⁵Surgical Oncology, UTMDACC, Houston, United States

**Introduction:** We reported the efficacy of ibrutinib with rituximab (IR) combination in relapsed MCL. Here we present the first efficacy/safety analysis of single center, phase II clinical trial of IR combination in untreated elderly pts with MCL.

**Methods:** Previously untreated elderly (>65 years) MCL pts (n=42) were enrolled in this study (NCT01880567). Pts with Ki-67% ≥ 50% and blastoid/pleomorphic histology were excluded. Pts received IR combination - ibrutinib 560 mg orally daily for 28 days (one cycle) continued until disease progression or discontinued for any reason. Rituximab was given on days 1, 8, 15 and 22 +/- 1 day by intravenous infusion (IV) at a fixed dose of 375 mg/m² (cycle 1), followed by rituximab on day 1 of every cycle starting in cycles 3 - 8. Following cycle 8, rituximab was given on day 1 of every other cycle for up to 2 years. The primary objective was to assess the safety and the efficacy. Among evaluable samples, minimal residual disease (MRD) by flow cytometry at best response and other molecular studies for clonal evolution at various time points were performed.

**Results:** The median age was 71 years (range 65-84), ECOG PS was (0/1) in 41 (98%) pts, 20% had high risk MIPI score, Ki-67% was low (<30%) in 30 (73%) and high (≥30-50%) in 11 (27%) pts, and 10% had complex karyotype. Median number of IR cycles was 19 (1-43). Best overall response (ORR) was 95% (69% CR, 26% PR, 5% stable disease). Median number of IR cycles to reach CR 4 (2-31). Thirty two patients had PET- based response assessment and all had CR (100%). MRD

<table><caption>TABLE 1 Summary of response and outcomes</caption><thead><tr><th>Best Response*</th><th>CR</th><th>PR</th><th>SD</th><th>ORR</th></tr></thead><tbody><tr><td>IR combination</td><td>69%</td><td>26%</td><td>5%</td><td>95%</td></tr><tr><td>#MRD negative at best response</td><td>65%</td><td></td><td></td><td></td></tr><tr><td colspan="5">Survival outcomes (months; range/95%CI)</td></tr><tr><td>Median follow up (range)</td><td colspan="4">24 (6-42)</td></tr><tr><td>Median PFS (range)</td><td colspan="4">Not reached</td></tr><tr><td>Median OS (range)</td><td colspan="4">Not reached</td></tr></tbody></table>

ORR overall response, CR complete response, PR partial response, SD is stable disease, * 4 patients discontinued treatment within first 3 cycles for grade 3 adverse events and one is on study and started treatment 2 months ago, # 37 pts were evaluable at best response for MRD

negative CR by flow cytometry was 65%. Overall, the median follow up was 24 months (6-42). Median PFS and OS were not reached. Among pts with low and high Ki-67%, median PFS was (not reached; p=0.28) and OS (not reached; p=0.02). Median duration on study was 19 months (range 1-39). Overall, 4 pts progressed (2 transformed to blastoid MCL) on study after taking IR for 4, 9, 13 and 32 months. Two pts died. At the time of last follow up, 24 pts remained on study and 18 (43%) discontinued therapy. Dose reduction was performed in 23 (55%) pts for various reasons. Most frequent grade 3-4 toxicities were 17% myalgias, 14% fatigue, 12% shortness of breath, 9% neutropenia and 5% new onset atrial fibrillation.

**Conclusions:** IR combination in elderly pts with MCL as a frontline treatment was very effective and safe. This strategy provides an excellent frontline alternate to chemotherapy in elderly pts with MCL.

**Keywords:** ibrutinib; mantle cell lymphoma (MCL).

**Disclosures:** Wang, M: Consultant Advisory Role: *Pharmacy* and Janssen.

012

IBRUTINIB WITH RITUXIMAB (IR) AND SHORT COURSE R-HYPERCVAD/MTX IS VERY EFFICACIOUS IN PREVIOUSLY UNTREATED YOUNG PTS WITH MANTLE CELL LYMPHOMA (MCL)

M. Wang<fnref n="1" /> | P. Jain<fnref n="1" /> | S. Zhang² | K. Nomie<fnref n="1" /> |

L. Wang² | O. Oriabure<fnref n="1" /> | G. Nogueras Gonzales<fnref n="3" /> |

L. Zhang<fnref n="1" /> | N. Wagner-Bartak⁴ | F. Hagemeister<fnref n="1" /> |

F. Samaniego<fnref n="1" /> | J. Westin<fnref n="1" /> | H.J. Lee<fnref n="1" /> |

L. Nastoupil<fnref n="1" /> | C. Ok⁵ | R. Kanagal-Shamanna⁵ |

W. Chen<fnref n="1" /> | S. Thirumurthi⁶ | D. Santos⁷ |

M. Badillo<fnref n="1" /> | L. Fayad<fnref n="1" /> | S. Neelapu<fnref n="1" /> | N. Fowler<fnref n="1" /> |

J. Romaguera<fnref n="1" />

<footnote n="1">¹Department of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston, United States; ²Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, United States;</footnote>

<footnote n="3">³Biostatistics, University of Texas MD Anderson Cancer Center, Houston,</footnote>
United States; ⁴Nuclear Medicine, University of Texas MD Anderson Cancer Center, Houston, United States; ⁵Hemato-pahtology, University of Texas MD Anderson Cancer Center, Houston, United States;
⁶Gastroenterology, University of Texas MD Anderson Cancer Center, Houston, United States; ⁷Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States

**Introduction:** Ibrutinib with rituximab (IR) combination induces durable responses in relapsed MCL. This is a single institution phase II trial of IR with short course (4 cycles) of R-HCVAD/R-MTX consolidation as frontline therapy in MCL.

**Methods:** Previously untreated young (≤65 years) MCL pts (n=50) were included. The study was registered with a ClinicalTrials.gov identifier number NCT02427620. Pts received IR induction (part-A), until they achieved complete remission (CR) up to a maximum of 12 cycles, followed by only 4 cycles of R-HCVAD/R-MTX (part-B). None of the patients received stem cell transplant or maintenance. The primary objective was to assess response rates after part-A. Among evaluable samples, minimal residual disease (MRD) by flow cytometry at best response, clonal evolution using circulating tumor DNA (ctDNA) at various time points, baseline somatic mutations and baseline gene expression profile (GEP) was performed.

**Results:** Overall, the median follow up was 36 months (10-42). Forty nine percent had high Ki-67 (≥30%), 72% had low risk MIPI score, one pt had TP53 mutation and 2 pts had aggressive MCL (one blastoid and one pleomorphic). Median number of cycles on IR was 6 (2-12). Overall response (ORR) on part-A of therapy was 100% (90% CR and 10% PR) and at the time of last follow up after completion of part A and part B, ORR was 100% (All CR). MRD negative CR rate assessed by bone marrow flow cytometry performed at best response at any phase of treatment was 91%. Overall, the median PFS and OS were not reached (3 year 89% and 100% respectively). Four pts had progressed after 17, 24, 34, 35 months of treatment (3 pts had Ki-67% ≥ 30% and one was blastoid MCL). None of the pts died. Grade 3-4 toxicities on part A were 4% myelosuppression and 8% each with fatigue, myalgia and rashes. GEP was done in 18 pts (2 PR, 16 CR on part A). Pts in PR had higher expression of HES1 while those in CR had significantly higher expression of CTLA4 and ITK genes compared to those in PR. Targeted DNA sequencing was done in 18 pts at baseline, one pt with PR had NSD2, KMT2C and another pt had TP53 mutations and had CR.

**Conclusions:** IR followed by short course R-HCVAD/R-MTX as frontline treatment induced durable and profound remissions in young MCL pts. This strategy demonstrated excellent efficacy and safety and minimized the exposure to chemotherapy.

**Keywords:** hyper-CVAD; ibrutinib; mantle cell lymphoma (MCL).

**Disclosures:** Wang, M: Consultant Advisory Role: Janssen, AstraZeneca, MoreHealth, Pulse Biosciences, AxImmune, Celgene, Juno Therapeutics, Pharmaceutics, IO Biotech, BioInvent; Stock Ownership: MoreHealth; Honoraria: Janssen, Dava Oncology, OMI, PeerView Institute for Medical Education (PVI); Research Funding: Janssen,

<table><caption>Table-1 Summary of response and outcomes</caption><thead><tr><th>Best Response</th><th>CR</th><th>PR</th><th>ORR</th></tr></thead><tbody><tr><td>Part A</td><td>90%</td><td>10%</td><td>100%</td></tr><tr><td>Part B*</td><td>100%</td><td>-</td><td>100%</td></tr><tr><td>#MRD negative at best response</td><td colspan="3">91%</td></tr><tr><td colspan="4">Survival outcomes (months; range/95%CI)</td></tr><tr><td>Median follow up (range)</td><td colspan="3">36 (10-42)</td></tr><tr><td>Median PFS (range)</td><td colspan="3">Not reached</td></tr><tr><td>Median OS (range)</td><td colspan="3">Not reached</td></tr></tbody></table>

ORR overall response, CR complete response, PR partial response, *2 pts did not take part B and one patient was not evaluable for response, # 43 pts were evaluable at best response for MRD

AstraZeneca, Acerta Pharma, Juno Therapeutics, Kite Pharma, BeiGene, Novartis, Celgene, BioInvent, Karus, Oncternal, Amgen.

## 013 AUTOLOGOUS STEM CELL TRANSPLANTATION IN FIRST REMISSION SIGNIFICANTLY PROLONGS PROGRESSION-FREE AND OVERALL SURVIVAL IN MANTLE CELL LYMPHOMA

A. Zoellner¹ | M. Unterhalt¹ | S. Stilgenbauer² |

K. Hübel³ | C. Thieblemont⁴ | B. Metzner⁵ |

H. Kluin-Nelemans⁶ | W. Hiddemann¹ | M. Dreyling¹ |

E. Hoster¹

¹Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; ²Department of Internal Medicine I, University Hospital of Homburg, Homburg, Germany; ³Department of Medicine I, University Hospital of Cologne, Cologne, Germany; ⁴Hemato-Oncology Department, Diderot University, Hôpital Saint-Louis, Paris, France; ⁵Department of Hematology/Oncology, University Hospital Oldenburg, Oldenburg, Germany; ⁶Hematology, Faculty of Medical Sciences, Groningen, Netherlands

**Introduction:** We report here the long term efficacy results (median follow up of 14 years) of the first randomized trial of the European MCL network which compared consolidation with myeloablative Radiochemotherapy followed by autologous stem cell transplantation (ASCT) to α-interferon maintenance (IFN) in first remission.

**Methods:** First results have been published previously (Dreyling et al., Blood 2005). In summary, between September 1996 and March 2004, 269 patients 65 years of age or younger from 129 institutions were randomized to either ASCT or IFN after induction with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), without or with Rituximab (R), or Mitoxantrone-Chlorambucil-Prednisone. R-CHOP was used in 32% of 232 patients with confirmed MCL.

**Results:** After a median follow-up of 14 years, 93 patients in the ASCT arm and 81 patients in the IFN arm, respectively, were evaluable for the intention to treat analysis of progression-free survival (PFS) and overall survival (OS) after responding to induction treatment. Clinical characteristics were comparable in both treatment groups with a
<figure><img src="image_5.png" /><figcaption>Figure 1: Description of progression-free (top) and overall survival (bottom) in remission from end of induction by treatment arm (random assignment) in European MCL 1</figcaption></figure>

median age of 55 years (34-65), 82% stage IV and 73% low, 20% intermediate, and 7% high risk according to Mantle cell lymphoma international prognostic index (MIPI). In patients receiving ASCT, the median PFS was 3.3 years, in patients receiving IFN the median PFS was 1.5 years (p < 0.0001). Furthermore, the median OS was significantly prolonged in patients receiving ASCT (7.5 years) than in patients receiving IFN (4.8 years) (p = 0.019). Adjusting for MIPI score and use of R-Chemotherapy, the hazard ratios for ASCT versus (vs.) IFN were 0.50 (95% CI, 0.36-0.69) for PFS and 0.66 (0.46-0.95) for OS. Cox regression analyses were performed to evaluate the differential effects of ASCT vs. IFN on PFS and OS according to induction treatment with R-Chemotherapy vs. Chemotherapy alone, adjusting for MIPI score. For patients treated without Rituximab the PFS hazard ratio for ASCT (n = 52) vs. IFN (n = 54) was 0.40 (0.26-0.61), in comparison to 0.72 (0.42-1.24) for patients treated with Rituximab (ASCT n = 41, IFN n = 27). For OS the hazard ratio for ASCT vs. IFN was 0.52 (0.33-0.82) for patients treated without Rituximab and 1.05 (0.55-1.99) for patients treated with Rituximab.

**Conclusion:** After a prolonged median follow up of 14 years the mature results of our trial confirm a significantly prolonged PFS and OS after ASCT in first remission of mantle cell lymphoma. However, there was only a non-significant trend for PFS and no difference in OS in the subset of patients treated with a Rituximab-containing induction therapy, potentially due to the reduced statistical power of this subgroup analysis. In the current study generation, the substitution of ASCT by the BTK inhibitor Ibrutinib is evaluated.

**Keywords:** autologous stem cell transplantation (ASCT); mantle cell lymphoma (MCL).

014
OBINUTUZUMAB PLUS DHAP FOLLOWED
BY AUTOLOGOUS STEM CELL
TRANSPLANTATION (ASCT) PLUS
OBINUTUZUMAB MAINTENANCE
PROVIDES A HIGH MRD RESPONSE RATE
IN UNTREATED MCL PATIENTS. RESULTS
OF LYMA-101 TRIAL, A LYSA GROUP
STUDY

S. Le Gouill¹ | A. Beldi-Ferchiou² | V. Cacheux³ |

G. Salles⁴ | D. Canioni⁵ | C. Bodet-Milin⁶ |

M. Alcantara⁷ | V. Delwail⁸ | T. Gastinne¹ |

C. Thieblemont⁹ | H. Maisonneuve¹⁰ |

T. Lamy de la Chapelle¹¹ | I. Oberic¹² |

K. Bouabdallah¹³ | V. Ribrag¹⁴ | M. Delfau-Larue² |

E. Macintyre¹⁵ | O. Hermine⁷

¹Hematology, CHU de Nantes, Nantes, France; ²Hematology Biology, Hôpital Henri Mondor, Creteil, France; ³Hematologie, CHU Clermont-Ferrand, Clermont-Ferrand, France; ⁴Hematology, HCL, Lyon, France; ⁵Pathology, Hôpital Necker, Paris, France; ⁶Nuclear Medecine, CHU de Nantes, Nantes, France; ⁷Hematologie, Hôpital Necker, Paris, France; ⁸Hematology Biology, CHU Poitiers, Poitiers, France; ⁹Hematology, Hôpital Saint-Louis, Paris, France; ¹⁰Hematology-Oncology, CH Roche-Sur-Yon, Roche-Sur-Yon, France; ¹¹Hematology, CHU de Rennes, Rennes, France; ¹²Hematology, Oncopole de Toulouse, Toulouse, France; ¹³Hematology, CHU Bordeaux, Bordeaux, France; ¹⁴Hematology, Institut Gustave Roussy, Villejuif, France; ¹⁵Hématologie Biologique, Hôpital Necker, Paris, France

**Introduction:** Achievement of prolonged minimal residual disease (MRD) negativity after both induction and ASCT is a strong independent prognostic marker in mantle cell lymphoma (MCL). A high-dose aracytine- (HA) and salt platinum-containing (P) chemotherapy regimen with Rituximab followed by autologous stem cell transplantation (ASCT) consolidation plus 3 years Rituximab maintenance is considered as a standard of care for untreated younger patients with MCL (Le Gouill et al. NEJM 2017). Obinutuzumab is a glycoengineered, type II, anti-CD20 monoclonal antibody designed to improve the antibody-dependent cell mediated cytotoxicity compared to Rituximab. in vitro experiments suggest that Obinutuzumab may provide better anti-MCL activity (Chiron et al., Blood 2016) than Rituximab but no in vivo data are available regarding Obinutuzumab in naive MCL patients.

**Methods:** The LYMA-101 study is a prospective and open phase II trial testing the effect of Obinutuzumab in untreated MCL patients under 66 years of age and eligible for intensive therapy. Induction consisted of 4 cycles of Obinutuzumab-DHAP (O-DHAP) before consolidation with ASCT (BEAM conditioning plus Obinutuzumab)
followed by Obinutuzumab maintenance for 3 years then Obinutuzumab on-demand for MRD positive patients. The LYMA-101 primary objective was the MRD negativity rate after 4 cycles of O-DHAP. MRD in the BM was assessed by IGH clonospecific or bcl1-JH PCR, and quantification with a sensitivity of at least 10⁻⁴ was reach by dd-PCR following Euro-MRD lymphoma group recommendations. We hypothesized that O-DHAP would be considered as an effective induction chemotherapy regimen if MRD negativity was ≥ 70%. We calculated that a minimum of 83 patients should be included (α risk of 0.05 and β of 0.20 one-sided test).

**Results:** We enrolled 86 patients between Nov 2016 and May 2018. One patient withdrew consent before starting treatment. Sixty-three patients (73.3%) were male and median age was 55.5 years (32-65). MIPI and MIPI-b risk scores were low in 47 (54.7%) and 9 (10.5%) cases, intermediate in 24 (27.9%) and 38 (44.2%) cases and high in 14 (16.3%) and 21 (24.4%) cases. Fifteen patients (17.4%) presented with a blastoid variant. At the time of analysis, median FU was 14 months (3.8-24.4). Twelve patients out of 85 were not evaluable for MRD, essentially due to purely nodal disease and no detectable MCL clone in PB or BM. Among the 73 MRD-informative patients, 62 reached MRD negativity in the BM (84.9%) while 6 were MRD positive after O-DHAP. The remaining 5 patients were not evaluated because 4 stopped treatment during induction due to AEs and one progressed then died. 72 patients underwent ASCT and 68 started Obinutuzumab maintenance. Twelve patients stopped treatment before ASCT (including disease progression in 2 cases and AE in 7 cases), 3 before maintenance (2 because of AE, one died during ASCT), and 9 during maintenance (including disease progression in one case, death in another, AE in 4 cases or other malignancies in 2 cases). In the whole population (n=85), 3 patients progressed, three died. At one year, PFS is 93.4% (IC95%, 84.7-97.2) and OS is 96% (IC95%, 88.1-98.7).

**Conclusion:** The Lyma-101 trial successfully achieved its primary endpoint (84.9% of MRD BM negativity after induction) and demonstrates the high efficacy of O-DHAP as induction chemotherapy regimen before ASCT with an unprecedented high level of MRD negativity, which predict better PFS and OS. Longer FU is needed to evaluate patient outcome after O-DHAP/ASCT/Obinutuzumab on-demand maintenance. However, both PFS and OS are highly encouraging at one year.

**Keywords:** mantle cell lymphoma (MCL); minimal residual disease (MRD); obinutuzumab.

**Disclosures:** Le Gouill, S: Consultant Advisory Role: Roche Genentech; Honoraria: Roche Genentech; Research Funding: Roche Genentech.

015
ZANUBRUTINIB IN PATIENTS WITH
RELAPSED/REFRACTORY MANTLE CELL
LYMPHOMA

Y. Song¹ | K. Zhou² | D. Zou³ | J. Zhou⁴ |
J. Hu⁵ | H. Yang⁶ | H. Zhang⁷ | J. Ji⁸ | W. Xu⁹ |

J. Jin¹⁰ | F. Lv¹¹ | R. Feng¹² | S. Gao¹³ |
D. Zhou¹⁴ | H. Guo¹⁵ | A. Wang¹⁵ | R. Elstrom¹⁶ |
J. Huang¹⁶ | W. Novotny¹⁶ | L. Han¹⁷ | J. Zhu¹

¹Department of Lymphoma, Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), Beijing, China; ²Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Beijing, China; ³Department of Lymphoma, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; ⁴Department of Hematology, Tongji Hospital, Tongji Medical College, Wuhan, China; ⁵Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China; ⁶Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China; ⁷Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; ⁸Department of Hematology, West China Hospital of Sichuan University, Chengdu, China; ⁹Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China; ¹⁰Department of Hematology, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China; ¹¹Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; ¹²Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China; ¹³Department of Hematology, Cancer Center, The First Hospital of Jilin University, Changchun, China; ¹⁴Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; ¹⁵Clinical Development, BeiGene (Beijing) Co., Ltd., Beijing, China; ¹⁶Clinical Development, BeiGene USA, Inc., San Mateo, United States; ¹⁷Biostatistics, BeiGene USA, Inc., San Mateo, United States

**Introduction:** Zanubrutinib is a selective and irreversible BTK inhibitor that has demonstrated potent inhibition of BTK in prior studies, with minimal, off-target inhibition of other kinases. We present updated safety and efficacy results from a phase 2 study of zanubrutinib in patients with R/R MCL.

**Methods:** In this single-arm, multicenter phase 2 study (ClinicalTrials.gov NCT03206970), oral zanubrutinib (160 mg BID) was given to R/R MCL patients until disease progression (PD) or unacceptable toxicity. Primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC) according to the 2014 Lugano Classification. Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DOR), investigator-assessed ORR, and safety.

**Results:** As of September 16, 2018, 86 R/R MCL patients were enrolled at 13 centers in China. Patient characteristics are summarized in the table. The median study follow-up was 13.9 months (range, 0.3-18.5 months) with treatment discontinuation in 29 (33.7%) patients, primarily due to PD (19 [22.1%]) and AE
<table><caption>Table. Patient Characteristics, Efficacy, and Safety</caption><thead><tr><th></th><th></th></tr></thead><tbody><tr><td>Patient Characteristics</td><td>N = 86</td></tr><tr><td>Median age, y (range)</td><td>60.5 (34-75)</td></tr><tr><td>Sex, n (%)</td><td></td></tr><tr><td>Male</td><td>67 (77.9)</td></tr><tr><td>Female</td><td>19 (22.1)</td></tr><tr><td>Time since first diagnosis of MCL (months)</td><td>30.1 (3.1-102.4)</td></tr><tr><td>Median no. of prior lines of therapy (range)</td><td>2 (1-4)</td></tr><tr><td>Bulky disease, n (%)</td><td></td></tr><tr><td>&gt;10 cm</td><td>7 (8.1)</td></tr><tr><td>&gt;5 cm</td><td>37 (43.0)</td></tr><tr><td>Blastic variant form of MCL, n (%)</td><td>12 (14.0)</td></tr><tr><td>Stage IV disease, n (%)</td><td>64 (74.4)</td></tr><tr><td>Intermediate/high-risk per MIPI-b, n (%)</td><td>72 (83.7)</td></tr><tr><td>Efficacy (Best Response)<sup>b</sup></td><td>N = 85<sup>a</sup></td></tr><tr><td>Overall response rate, n (%); (95% CI)</td><td>72 (84.7); (75.3, 91.6)</td></tr><tr><td>Complete response, n (%)</td><td>65 (76.5)</td></tr><tr><td>Partial response, n (%)</td><td>7 (8.2)</td></tr><tr><td>Stable disease, n (%)</td><td>1 (1.2)</td></tr><tr><td>Progressive disease, n (%)</td><td>8 (9.4)</td></tr><tr><td>Discontinued prior to first response assessment, n (%)</td><td>4 (4.7)</td></tr><tr><td>Safety, n (%)</td><td>N = 86</td></tr><tr><td>Any TEAE</td><td>83 (96.5)</td></tr><tr><td>Any grade ≥3 TEAE</td><td>34 (39.5)</td></tr><tr><td>TEAE leading to zanubrutinib discontinuation</td><td>9 (10.5)</td></tr><tr><td>Grade 5 TEAE</td><td>5 (5.8)</td></tr></tbody></table>

(8 [9.3%]). In 85 efficacy evaluable patients, investigator-assessed ORR was 84.7%, and 65 (76.5%) patients achieved complete response. The median DOR was 14.0 months (range, 2.32-14.0 months). The median PFS was 16.7 months (range 0.0+ to 16.7+ months). The ORR was generally consistent across subgroups analyzed (MIPI [Mantle Cell International Prognostic Index], previous therapy, blastoid variant, etc). The most common (≥15%) treatment-emergent AEs (TEAEs) included decreased neutrophil count (41.9%), rash (33.7%), upper respiratory tract infection (33.7%), decreased white blood cell (WBC) count (26.7%), decreased platelet count (25.6%), hypokalemia (16.3%), and diarrhea (15.1%). Grade 3 TEAEs reported in >2 patients included decreased neutrophil count (16.3%), decreased WBC count, anemia, lung infection (each 5.8%), decreased platelet count (4.7%), and hypertension (3.5%). The most frequent hemorrhage events were hematuria and petechiae/purpura/contusion (4.7% each, grade 1/2). Major hemorrhage (serious or grade 3 bleeding or central nervous system bleeding of any grade) was reported in 2 patients (2.3%). No cases of atrial fibrillation/ flutter, second primary malignancies or tumor lysis syndrome were reported. TEAEs leading to treatment discontinuation in nine (10.5%) patients included infection, lung infection, pneumonia, upper gastrointestinal hemorrhage, road traffic accident, cerebral hemorrhage, interstitial lung disease (n=1 each), and decreased platelet count (n=2).

**Conclusions:** Updated results of this study further substantiated the high activity of zanubrutinib resulting in a high rate of durable response in R/R MCL. The safety profile was consistent with previous reports of zanubrutinib treatment.

**Keywords:** BTK inhibitors; mantle cell lymphoma (MCL); zanubrutinib.

**Disclosures:** Guo, H: Employment Leadership Position: Executive Director of BeiGene; Stock Ownership: Own BeiGene Stock. Wang, A: Employment Leadership Position: Medical Director of BeiGene; Stock Ownership: Own BeiGene Stock. Elstrom, R: Employment Leadership Position: Employee of BeiGene. Huang, J: Employment Leadership Position: CMO Hematology of BeiGene. Novotny, W: Employment Leadership Position: Employee of BeiGene; Stock Ownership: Own BeiGene Stock.

016
OUTCOMES IN FIRST RELAPSED-
REFRACTORY YOUNGER PATIENTS WITH
MANTLE CELL LYMPHOMA: RESULTS
FROM THE MANTLE-FIRST STUDY

C. Visco¹ | A. Di Rocco² | M.C. Tisi¹ | L. Morello³ |

A. Evangelista⁴ | V.R. Zilioli⁵ | C. Rusconi⁵ |

S. Hohaus⁶ | R. Sciarra⁷ | A. Re⁸ | C. Tecchio⁹ |

<footnote>*One patient was not evaluable for response due to a lack of central pathologic confirmation of MCL.</footnote>

<footnote><sup>b</sup>IRC-assessed efficacy will be reported later.</footnote>

<footnote>MIPI-b, Mantle Cell International Prognostic Index-biologic</footnote>
A. Chiappella¹⁰ | A. Marin-Niebla¹¹ | R. McCulloch¹² | G. Gini¹³ | T. Perrone¹⁴ | L. Nassi¹⁵ | E. Pennese¹⁶ | P.M. Stefani¹⁷ | M.C. Cox¹⁸ | V. Bozzoli¹⁹ | A. Fabbri²⁰ | V. Polli²¹ | S. Ferrero²² | I.A. De Celis²³ | A. Sica²⁴ | L. Arcaini⁷ | M. Balzarotti³ | S. Rule¹² | U. Vitolo¹⁰

¹Medicine, Section of Hematology, University of Verona, Verona, Italy;
²Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy;
³Hematology, Humanitas Clinical and Research Center, Rozzano, Italy;
⁴Clinical Epidemiology, Città della Salute e della Scienza and CPO Piemonte, Torino, Italy;
⁵Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy;
⁶Institute of Hematology, Policlinico Gemelli Foundation, Catholic University of the Sacred Heart, Roma, Italy;
⁷Haematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;
⁸Hematology, Spedali Civili, Brescia, Italy;
⁹Medicine, Section of Hematology and Bone Marrow Transplant, University of Verona, Verona, Italy;
¹⁰Hematology, Città della salute e della scienza University Hospital, Torino, Italy;
¹¹Hematology, Vall d'Hebron Institut d'Oncologia (VHIO), Barcelona, Spain;
¹²Haematology, University of Plymouth and Derriford Hospital, Plymouth, United Kingdom;
¹³Hematology, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy;
¹⁴Hematology, University of Bari, Bari, Italy;
¹⁵Hematology, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy;
¹⁶Hematology, UOSD "Centro Diagnosi e Terapia dei Linfomi", PO Santo Spirito, Pescara, Italy;
¹⁷Hematology, Ca' Foncello Hospital, Treviso, Italy;
¹⁸Hematology, AOU Sant'Andrea, Rome, Italy;
¹⁹Hematology, P.O. V. Fazzi, Lecce, Italy;
²⁰Hematology, Azienda Ospedaliera Universitaria Senese & University of Siena, Siena, Italy;
²¹Hematology, Ospedale degli Infermi, Rimini, Italy;
²²Molecular Biotechnologies and Health Sciences, University of Torino/AOU "Città della Salute e della Scienza di Torino", Torino, Italy;
²³Hematology, AUSLL/IRCCS Santa Maria Nuova Hospital, Reggio Emilia, Italy;
²⁴Hematology, Policlinico di Napoli, Napoli, Italy

**Introduction:** Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population with poor outcome, where no standard therapy exists. There is a paucity of large-scale data in relapsed or refractory (r/r) MCL.

**Methods:** MANTLE-FIRST, an international, retrospective study, evaluated outcomes in patients with MCL who had progressive disease or first relapse when treated upfront with high dose cytarabine (HDAC), followed by autologous stem cell transplantation if appropriate. Response rates, overall survival (OS), and progression-free survival (PFS) were estimated from the time of initiation of salvage therapy. The previously defined threshold of 24 months since MCL initial diagnosis was used to define patients as having early- or late- first relapse or progression (POD).

**Results:** Overall, 258 patients with r/r MCL were included, with a median follow-up from time of relapse or progression of 38 months (range 1-122). Second line regimens consisted of rituximab bendamustine (R-B) in 22%, rituximab, bendamustine,

<figure><img src="image_6.png" /></figure>

Median PFS (months): ibrutinib 24±14; R-BAC 25±6; R-B 12±1; other regimens 7±2.
P=0.11 between R-BAC and R-B; p=0.07 between ibrutinib and R-B;
P=0.86 between ibrutinib and R-BAC; p=0.001 between ibrutinib and other regimens;
P=0.06 between R-B and other regimens; p=0.0002 between R-BAC and other regimens.

cytarabine (R-BAC) in 29%, ibrutinib in 18%, and other regimens in 31%. Overall response rate was higher in ibrutinib and R-BAC treated patients (79% for both), as compared to R-B (62%), or other regimens (30%). Complete response (CR) were significantly higher in patients treated with R-BAC (63%) than with R-B (43%, p=0.02), ibrutinib (34%, p=0.002), or other approaches (22%, p<0.0001). Median OS and PFS for all patients were 34±5 and 13 ±8 months, respectively. PFS curves according to second line therapy are shown in **Figure 1**. For patients with early-POD (n=126), outcomes were consistently poor, irrespectively of administered second line therapy (median OS 10±1 months), unless for those receiving allogeneic transplant (n=27, median OS 63±24 months). Ibrutinib was associated with longer PFS and OS (10±1 and 30 ±13, respectively), compared to immunochemotherapy (6±2 and 12±2 months, p=0.09 and p=0.08). For patients with late-POD (n=132), median OS was 74±9 months, and PFS was 34±5. Ibrutinib (not reached), R-BAC (not reached) and R-B (73±21) had similar significant OS advantage, compared to other regimens (41 ±11, p=0.03). Ibrutinib and R-BAC had similar PFS of 52±18 and 53±22 months, respectively, while R-B was associated with shorter PFS of 31±3 months, although not statistically significant, and other regimens with median PFS of 13±1 months (p<0.0001). At multivariate analysis, factors significantly and independently associated to a reduction of the risk of death were achievement of CR after second line regimens (HR 0,19), allogeneic transplant (HR 0,40), ibrutinib second line therapy (HR 0,47) and late-POD (HR 0,49).

**Conclusions:** MANTLE-FIRST is the largest patient-level pooled retrospective analysis to characterize survival for a population of HDAC treated first r/r MCL. Time to POD confirmed its importance for treatment decisions, with allo-transplant being the only curative option in early-POD. Ibrutinib second line was associated with OS advantage, while R-BAC induced higher CR rate and similar PFS.

**Keywords:** Bendamustine; ibrutinib; mantle cell lymphoma (MCL).
FOCUS ON... SESSION: PET IMAGING

017
A GENE EXPRESSION-BASED SCORE TO PREDICT INTERIM PET POSITIVITY IN HODGKIN LYMPHOMA PATIENTS TREATED WITH ABVD

B. Donati<fnref n="1" /> | M. Casali<fnref n="2" /> | A. Fama³ | B. Puccini<fnref n="4" /> |

M. Zanelli<fnref n="5" /> | R. Valli<fnref n="5" /> | R. Santi<fnref n="6" /> | F. Vergoni<fnref n="6" /> |

A. Ruffini<fnref n="7" /> | V. Berti<fnref n="8" /> | L. Rigacci<fnref n="9" /> | F. Merli³ |

A. Ciarrocchi<fnref n="1" /> | S. Luminari³

**Introduction:** Response-adapted therapy through the use of FDG-PET after 2 cycles of ABVD (interim PET-iPET) is an effective strategy in Hodgkin's Lymphoma (HL). However, this approach may cause 2 months of suboptimal treatment. The objective of this study was to use gene-expression profiling to build and validate a model to predict iPET positivity (iPET+).

**Methods:** Consecutive untreated patients (pts) with stage I-IV HL with available diagnostic tumor sample who underwent iPET after two cycles of ABVD were identified from the Reggio Emilia Hematology unit and used to define the training set. A validation set was identified from the hematology unit in Firenze using the same criteria. Expression of 770 immune related genes was analyzed by digital expression profiling (Nanostring Technology). Conventional clinical and laboratory parameters were collected. iPET was centrally reviewed according to the five-point Deauville scale (5PS), and was used as primary study endpoint. Clinical events were used as secondary endpoint and included treatment change for iPET+ cases and relapse/progression for other cases. An iPET+ predictive model was derived by multivariate regression analysis and assessed in a validation set.

**Results:** A training set of 121 and a validation set of 113 pts were identified, with 23 iPET+ cases in each group. Median age of the training cohort was 38 years (18 to 75); 63 (52.1%), 19 (15.7%) and 39 (32.2%) had stage I-II, III and IV respectively. iPET+ HLs have a distinctive transcriptional profile at diagnosis that discriminate these lesions from iPET-. A list of 13 genes was found significantly associated with iPET+. This signature comprises two functionally distinct, stromal-related nodes. Lymph mono-ratio (LMR) was also associated

to iPET+. In the training cohort a 5-gene and LMR integrated score predicted interim iPET+ (AUC0.88 95%CI, 0.80-0.96). Model score was used to divide the training cohort into quartiles showing that the vast majority of iPET+ patients segregated within Q4th (Q4th -76.2%, Q3th -9.5%, Q2th -14.2% and Q1th -0%). Model performance was confirmed in the validation set (AUC0.67 95%, 0.47-0.84). Furthermore, score-based quartile separation in this cohort, confirmed the preferential distribution of iPET+ pts within Q4th. Merging the training and validation set, 34 events were identified out of 172 pts (16 pts who underwent therapy escalation after iPET+ and 18 with relapse). iPET score was higher in pts with event vs those without event. Correlation of iPET score with pts survival was not informative because the adoption of intensified therapies in iPET+ cases (46% of iPET+) likely corrected the higher risk of progression in these pts.

**Conclusions:** In HL interim metabolic response measured with PET after 2 ABVD cycles is associated with a genetic signature and can be predicted applying an integrated gene-based model on the diagnostic biopsy.

**Keywords:** ABVD; gene expression profile (GEP); Hodgkin lymphoma (HL).

018
PERSISTENT MEDIASTINAL POSITRON EMISSION TOMOGRAPHY (PET)-POSITIVITY AFTER FRONTLINE THERAPY FOR HODGKIN LYMPHOMA IS BEST MANAGED BY CLOSE OBSERVATION

M. Novo<fnref n="1" /> | G.S. Nowakowski<fnref n="1" /> | T.M. Habermann<fnref n="1" /> |

T.E. Witzig<fnref n="1" /> | I.N. Micallef<fnref n="1" /> | P.B. Johnston<fnref n="1" /> |

D.J. Inwards<fnref n="1" /> | K. Ristow<fnref n="1" /> | J.R. Young<fnref n="2" /> | S.M. Ansell<fnref n="1" />

**Introduction:** Residual FDG PET uptake in the mediastinum after frontline therapy for classical Hodgkin lymphoma (cHL) is a challenging situation as it is difficult to distinguish between persistent disease and inflammatory changes post treatment. Thus, we analyzed the practice patterns at a single institution to determine how often a biopsy of the site was informative, and whether it influenced patient management and outcome.

**Methods:** We retrospectively reviewed all cHL treated at the Hematology Department of Mayo Clinic in Rochester MN between January 2003 and December 2018. Cases with a mediastinal mass at diagnosis (largest diameter ≥5 cm) and isolated PET-positivity at that site after standard frontline therapy were included into the study. Clinical approach adopted and outcomes were analyzed and an independent radiological review of PET images was performed.

**Results:** Among 1060 cHL evaluated, 37 were eligible for the study. A mediastinal biopsy was performed in 19/37 cases (group 1): 9/19

<footnote n="1">¹Laboratory of Translational Research, AUSL IRCCS, Reggio Emilia, Italy;</footnote>

<footnote n="2">²Nuclear Medicine, AUSL IRCCS, Reggio Emilia, Italy; ³Hematology, AUSL IRCCS, Reggio Emilia, Italy;</footnote>

<footnote n="4">⁴Hematology, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy;</footnote>

<footnote n="5">⁵Pathology, AUSL IRCCS, Reggio Emilia, Italy;</footnote>

<footnote n="6">⁶Pathological Histology and Molecular Diagnostics, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy;</footnote>

<footnote n="7">⁷Hematology, GRuppo Amici dell'Ematologia Foundation_GRADE, Reggio Emilia, Italy;</footnote>

<footnote n="8">⁸Nuclear Medicine, University of Firenze, Firenze, Italy;</footnote>

<footnote n="9">⁹Hematology and Stem Cell Transplant, AO San Camillo Forlanini, Roma and Hematology of Azienda Ospedaliero Universitaria Careggi, Firenze, Italy</footnote>

<footnote n="1">¹Hematology, Mayo Clinic, Rochester, MN, United States; ²Radiology, Mayo Clinic, Rochester, MN, United States</footnote>
<figure><img src="image_7.png" /><figcaption>Figure 1. flow chart with summarized clinical approaches.</figcaption></figure>

(47%) were positive for cHL and all underwent salvage chemotherapy followed by autologous stem cell transplant (CT+ASCT) (group 1a). Among biopsy-negative cases (group 1b), 4/10 were observed and 6/10 received radiotherapy (RT) consolidation. Among the non-biopsied cases (group 2), 10/18 were observed (group 2a), 7/18 received RT (group 2b), and 1/18 underwent CT+ASCT (group 2c). Patients of group 2a had a repeat PET scan after a median time of 13 weeks (range 4-35) and then only 7/10 showed persistent FDG uptake or progression disease. 6/6 biopsies performed at this time were positive and all cases received CT+ASCT. No biopsy was done in 1/7 case considered to be thymic rebound. Among patients of group 1a, 2a and 2c receiving CT-ASCT, complete remission (CR) was obtained in 11/16 (69%); 8/13 (61%) patients from group 1b or 2b receiving consolidative RT remained in CR; 2/4 cases observed after a negative biopsy subsequently progressed; 3/10 cases of group 2a converted to PET negativity and remained in CR. (Fig 1) With a median follow up of 38.4 months, no survival difference between groups 1 and 2 was observed.

On radiological review of 34/37 patients at the end of therapy, Deauville scores (DS) of the PET images were as follows: 3 cases DS2, 4 DS3, 12 DS4, 12 DS5, 3 thymic rebound (DSX). The rate of relapse was 1/3 (33%) for DS2, 1/4 (25%) for DS3, 4/12 (33%) for DS4, 10/12 (83%) for DS5 and 1/3 (33%) for DSX.

**Conclusions:** Within the limitations of this small retrospective cohort, biopsy of post-treatment persistent mediastinal PET-positivity in cHL patients is positive in less than half the cases and DS was relatively unhelpful in selecting patients with potentially refractory disease. We conclude that adopting a "wait-and-see" strategy with a repeat PET scan reassessment 8-12 weeks later increases the likelihood that the subsequent biopsy will be positive without compromising the outcome and may be the preferred approach.

**Keywords:** classical Hodgkin lymphoma (cHL); Deauville's criteria; F-18-fluorodeoxyglucose (FDG).

019

HIGH TOTAL METABOLIC TUMOR VOLUME AT BASELINE ALLOWS TO DISCRIMINATE FOR SURVIVAL PATIENTS IN RESPONSE AFTER R-CHOP: AN ANCILLARY ANALYSIS OF THE REMARC STUDY

A. Cottereau¹ | L. Vercellino² | O. Casasnovas³ |

H. Tilly⁴ | P. Feugier⁵ | C. Fruchart⁶ | L. Roulin⁷ |

L. Oberic⁸ | G. Pica⁹ | V. Ribrag¹⁰ | J. Abraham¹¹ |
M. Simon¹² | H. Gonzalez¹³ | R. Bouabdallah¹⁴ |

O. Fitoussi¹⁵ | C. Sebban¹⁶ | A. Lopez¹⁷ |

M. Macro⁶ | L. Sahnes¹⁸ | F. Morschhauser¹⁹ |

J. Trotman²⁰ | B. Corront²¹ | B. Choufi²² |

S. Snauwaert²³ | P. Godmer²⁴ | C. Copie-Bergman²⁵ |

J. Briere²⁶ | G. Salles²⁷ | P. Gaulard²⁵ |

M. Meignan²⁸ | C. Thieblemont²⁹

¹Medecine Nucleaire, APHP, Cochin, Paris, France; ²Medecine Nucleaire, APHP, Saint-Louis Hospital, Paris, France; ³Hematology, CHU Dijon, Dijon, France; ⁴Hematology, Centre H. Becquerel, Rouen, France;

⁵Hematology, CHU Brabois - Nancy, Nancy, France; ⁶Hematology, CHU Caen, Caen, France; ⁷Hematology, APHP, Henri Mondor Hospital, Créteil, France; ⁸Hematology, CHU Toulouse, Toulouse, France; ⁹Hematology, CHU Annecy, Annecy, France; ¹⁰Hematology, IGR, Villejuif, France;

¹¹Hematology, CHU Limoges, Limoges, France; ¹²Hematology, CH Valenciennes, Valenciennes, France; ¹³Hematology, CH Pontoise, Pontoise, France; ¹⁴Hematology, IPC, Marseille, France; ¹⁵Hematology, Hopital Bordeaux Nord, Bordeaux, France; ¹⁶Hematology, Centre L. Berard, Lyon, France; ¹⁷Hematology, IOB, Barcelona, Spain;

¹⁸Hematology, CH Perpignan, Perpignan, France; ¹⁹Hematology, CHU Lille, Lille, France; ²⁰Hematology, Concord Hospital, Sydney, Australia;

²¹Hematology, CH Annecy, Annecy, France; ²²Hematology, CH Boulogne, Boulogne, France; ²³Hematology, AZ Sint-Jan, Brugge, Belgium;

²⁴Hematology, CH Vannes, Vannes, France; ²⁵Pathology, APHP, Henri Mondor Hospital, Créteil, France; ²⁶Pathology, APHP, Saint-Louis Hospital, Paris, France; ²⁷Hematology, CHU Lyon, Pierre-Benite, France;

²⁸Medecine Nucleaire, APHP, Henri Mondor Hospital, Créteil, France;

²⁹Hematology, APHP, Saint-Louis Hospital, Paris, France

**Introduction:** High total metabolic tumor volume (TMTV) measured on 18F-FDG PET/CT before R-CHOP has been shown to be significantly associated with inferior progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma. The REMARC study (NCT01122472) showed a significantly better progression-free survival (PFS) in 650 patients responding to R-CHOP treated with maintenance therapy with lenalidomide (LEN) versus placebo (PBO), but no difference in OS was observed. The aim was to analyze the prognostic impact of baseline TMTV together with biological profile.

**Methods:** TMTV was computed on baseline PET/CT using the 41% SUVmax method. The optimal TMTV cut-off for PFS and OS was determined by Receiver Operating Curve and X-tile analyses and confirmed by a training validation method. A subset of patients (n = 192) was classified as GCB or non-GCB profile, and with MYC or BCL2 by FISH. Survival was estimated using Kaplan Meier (KM) curves. Analyses were performed on the evaluable population (n=301/650) and each arm, with 146 pts on PBO and 155 pts on LEN.

**Results:** Clinical characteristics were similar to the overall population. After a median 5 years follow-up, 4y-PFS was 73% and 4y-OS was 85%. Median baseline TMTV was 238 cm³ (Q1-Q3;78,523). The optimal TMTV cut-off was 220 cm³ for PFS and OS. Patients with TMTV

>220 vs ≤220 cm³ presented with worse ECOG performance status (ECOG ≥2: 21% vs 11.5%, p=0.029), higher Ann Arbor stage (stage III-IV: 94% vs 87%, p=0.043), more extra-nodal sites (>1: 63.5% vs 39%, p<0.001), more frequently elevated LDH (74% vs 45%, p<0.001), higher IPI (IPI 3-5: 85% vs 58%, p=10⁻³), and higher aalPI (score 2-3: 74% vs 40%, p=10⁻³). In all evaluated patients, a significant impact of TMTV was observed for PFS (p=2.10⁻⁴) and OS (p=10⁻⁴). Patients with high TMTV>220 vs low TMTV≤220, had a 4-year PFS of 56% vs 82% and OS of 74% vs 92% respectively. This prognostic impact of a high baseline TMTV on PFS (HR=2.2; 95% CI, 1.4-3.5) and OS (HR=3.2; 95% CI, 1.5-6.6) was maintained in both PBO and LEN arms. As demonstrated in the original report, GCB/nonGCB profile had no significant impact on PFS and OS, regardless of TMTV. BCL2 impacted PFS and could be stratified by TMTV. MYC had no impact on PFS and OS. In multivariate analysis, baseline TMTV was the most powerful parameter associated with inferior PFS and OS, compared to aalPI and treatment arm.

**Conclusion:** TMTV measured on baseline PET/CT is the strongest prognosticator of outcome in DLBCL, even in patients in responding after R-CHOP. High TMTV at baseline was significantly associated with inferior PFS and OS in patients receiving either PBO or LEN.

**Keywords:** diffuse large B-cell lymphoma (DLBCL); positron emission tomography (PET).

## 020
BASELINE TOTAL METABOLIC TUMOUR VOLUME IS HIGHLY PROGNOSTIC FOR REFRACTORINESS TO IMMUNOCHEMOTHERAPY IN DLBCL: AN ANALYSIS OF THE PHASE 3 GOYA TRIAL

M. Trněný¹ | I. Canales Ruiz² | M. Martelli³ |

L.H. Sehn⁴ | U. Vitolo⁵ | H. Brown⁶ | T. Nielsen² |

G. Sellam² | L. Kostakoglu⁷

¹1st Department of Medicine - Department of Haematology, Charles University, General Hospital, Prague, Czech Republic; ²Product Development Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland; ³Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy; ⁴Medical Oncology, University of British Columbia, Vancouver, Canada; ⁵Department of Oncology and Haematology, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy; ⁶on assignment to Roche Products Ltd, Welwyn Garden City, United Kingdom; ⁷Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, United States

**Introduction:** The prognosis for patients (pts) with diffuse large B-cell lymphoma (DLBCL) refractory to treatment with standard frontline rituximab (R)-based immunochemotherapy is poor, and there are currently no clinical tools to identify these pts. This exploratory analysis investigated primary refractoriness in previously untreated pts with DLBCL from the phase 3 GOYA trial (NCT01287741).
<table><caption>Table. Baseline patient and disease characteristics and their association with primary refractoriness in a univariate analysis</caption><thead><tr><th rowspan="2">Characteristic*</th><th colspan="2">At baseline</th><th rowspan="2">Association with<br>primary<br>refractoriness<br>(p-value)</th></tr><tr><th>Overall population<br>(n=1418)</th><th>Primary refractory<br>patients<br>(n=113)</th></tr></thead><tbody><tr><td><strong>Treatment arm</strong></td><td></td><td></td><td>0.1304</td></tr><tr><td>R-CHOP</td><td>712 (50.2)</td><td>63 (55.8)</td><td></td></tr><tr><td><strong>Ann Arbor stage</strong></td><td></td><td></td><td>0.0176</td></tr><tr><td>III/IV</td><td>1076 (75.9)</td><td>95 (84.1)</td><td></td></tr><tr><td><strong>IPI risk category</strong></td><td></td><td></td><td>0.0092</td></tr><tr><td>High</td><td>220 (15.5)</td><td>23 (20.4)</td><td></td></tr><tr><td><strong>Median SPD, mm² (range)</strong></td><td>4425 (0–510000)</td><td>5968.05 (240–47104)</td><td>0.0120</td></tr><tr><td><strong>Bulky disease (≥7.5 cm)</strong></td><td>523 (37.0)</td><td>51 (45.1)</td><td>0.0231</td></tr><tr><td><strong>Extranodal involvement</strong></td><td>952 (67.1)</td><td>79 (69.9)</td><td>0.0067</td></tr><tr><td><strong>Elevated LDH</strong></td><td>816 (57.7)</td><td>80 (71.4)</td><td>0.0016</td></tr><tr><td><strong>Hb &lt;LLN</strong></td><td>736 (52.5)</td><td>69 (61.1)</td><td>0.0193</td></tr><tr><td><strong>TMTV*</strong></td><td></td><td></td><td>0.0093</td></tr><tr><td>Q1 (1–103 mL)</td><td>283 (21.9)</td><td>18 (15.9)</td><td></td></tr><tr><td>Q2 (102–336 mL)</td><td>283 (21.9)</td><td>14 (12.4)</td><td></td></tr><tr><td>Q3 (336–842 mL)</td><td>284 (22.0)</td><td>18 (15.9)</td><td></td></tr><tr><td>Q4 (841–8282 mL)</td><td>284 (22.0)</td><td>33 (29.2)</td><td></td></tr><tr><td>Missing</td><td>158 (12.2)</td><td>30 (26.6)</td><td></td></tr><tr><td><strong>Time since diagnosis</strong></td><td></td><td></td><td>0.0234</td></tr><tr><td>&lt;1 month</td><td>895 (63.4)</td><td>76 (67.3)</td><td></td></tr><tr><td><strong>CD4+ T cell (CD3+ CD4+) count</strong></td><td>-</td><td>-</td><td>0.1114</td></tr><tr><td><strong>NK cell (CD16+ CD56+) count</strong></td><td>-</td><td>-</td><td>0.0405</td></tr></tbody></table>

**Methods:** Pts were randomised 1:1 to receive either obinutuzumab (G-) or R-CHOP (G 1000 mg cycle [C]1 day [D]1, 8 and 15, and C2–8 D1; R 375 mg/m² C1–8 D1; CHOP 6 or 8 cycles every 21 days). Primary refractory pts were defined as those with no metabolic response or progressive metabolic disease (PMD) at end of treatment (EOT) by Independent Review Committee using Lugano PET criteria, or progression (PD)/death due to PD before EOT by investigator. The association between baseline characteristics and primary refractoriness was analysed using univariate Cox regression; significant covariates (p≤0.15, Wald test) were assessed via multivariate analysis using backward elimination (significance cut-off p<0.05).

**Results:** Of 1418 pts in GOYA, 113 (8.0%) were identified as primary refractory (median age 61 years; 54% male). At baseline, more primary refractory pts presented with unfavourable disease characteristics versus the overall GOYA population (Table). Median overall survival (OS) was 14 months for primary refractory pts, with a 2-year OS of <30% versus 83.9% (G-CHOP) and 83.6% (R-CHOP) in the overall GOYA population. In a univariate analysis, multiple baseline covariates were significantly associated with primary refractoriness (p≤0.15; Table); tumour metabolic total volume (TMTV) remained the only independent adverse prognostic factor in multivariate analysis (p=0.0094). Across the 4 TMTV quartiles (Q), the proportion of primary refractory pts (33/284;

11.6%) found in Q4 was almost twice that in the other quartiles (18/283 [6.4%] in Q1, 4.9% [14/283] in Q2, 6.3% [18/286] in Q3), and a receiver operating characteristics analysis identified a TMTV >523.8 mL as the optimal cut-off for identification of primary refractory pts.

**Conclusions:** TMTV was the only independent prognostic factor for primary refractoriness in previously untreated pts with DLBCL, suggesting that responsiveness to immunochemotherapy is associated with tumour burden. Considering TMTV as a prognostic factor may assist in the identification of high-risk pts who may benefit from an alternative therapeutic strategy.

**Acknowledgment:** Third-party medical writing assistance, under the direction of Marek Trněný and Irene Canales Ruiz, was provided by Zoe Toland and Helen Cathro of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.

This abstract was previously submitted to EHA 2019.

**Keywords:** diffuse large B-cell lymphoma (DLBCL); immunochemotherapy; obinutuzumab.

**Disclosures:** Trněný, M: Consultant Advisory Role: Takeda, Bristol-Myers Squibb, Incyte, Abbvie, Amgen, Roche, Gilead Sciences, Janssen, Celgene, MorphoSys; Honoraria: Janssen, Gilead Sciences, Takeda, Bristol-Myers Squibb, Amgen, Abbvie, Roche, MorphoSys, Incyte; Other Remuneration: Expenses: Gilead Sciences, Takeda, Bristol-Myers Squibb, Roche, Janssen,

<footnote>*All characteristics n (%) unless otherwise specified; †In the GOYA intent-to-treat population, n=1292 Hb, haemoglobin; IPI, International Prognostic Index; LDH, lactate dehydrogenase; LLN, lower limit of normal; NK, natural killer; R, rituximab; SPD, sum of the product of diameters of up to 6 target lesions; TMTV, total metabolic tumour volume</footnote>
Abbvie. **Martelli, M:** Consultant Advisory Role: Roche, Gilead, Novartis, Servier, Sandoz, Janssen, Celgene; Other Remuneration: Speakers' Bureau: Roche, Gilead, Servier, Sandoz, Janssen, Celgene; Expenses: Roche (ASH).

**Sehn, L:** Consultant Advisory Role: Abbvie, Amgen, Roche Genetech, Apobiologix, AstraZeneca, Acerta, Celgene, Gilead, Janssen, Kite, Karyopharm, Lundbeck, Merck, MorphoSys, Seattle Genetics, Teva, Takeda, TG Therapeutics; Honoraria: Abbvie, Amgen, Roche Genetech, Apobiologix, AstraZeneca, Acerta, Celgene, Gilead, Janssen, Kite, Karyopharm, Lundbeck, Merck, MorphoSys, Seattle Genetics, Teva, Takeda, TG Therapeutics; Research Funding: Roche Genetech. **Vitolo, U:** Consultant Advisory Role: Janssen, Celgene, Roche; Research Funding: Celgene, Roche; Other Remuneration: Speakers' Bureau: Roche, Celgene, Takeda, Gilead, Servier, Sandoz, Janssen; Expenses: Roche, Janssen, Celgene, Gilead.

**Brown, H:** Employment Leadership Position: Employed by PAREXEL, external business partner with Roche Products Ltd, Welwyn, UK. **Nielsen, T:** Employment Leadership Position: Roche; Stock Ownership: Roche.

**Sellam, G:** Employment Leadership Position: Roche; Stock Ownership: Roche. **Kostakoglu, L:** Consultant Advisory Role: Roche Genetech, BeiGene; Honoraria: Novartis.

## 021
# RADIOMICS INCREASE THE PROGNOSTIC VALUE OF CLINICAL AND PET RISK FACTORS IN DLBCL: RESULTS FROM THE PHASE 3 GOYA STUDY

**S. Chauvie<fnref n="1" />** | **F. Dalmasso<fnref n="1" />** | **L. Pierce²** | **U. Vitolo³** |

**M. Martelli⁴** | **L.H. Sehn⁵** | **M. Trněný⁶** |

**T. Nielsen⁷** | **D. Sahin⁷** | **C. Lee⁸** | **F. Mattiello⁷** |

**P. Berchialla⁹** | **P.E. Kinahan²** | **L. Kostakoglu¹⁰**

**Introduction:** We investigated whether quantitative image texture analysis that measures tumour heterogeneity, i.e. radiomics, improves the prognostic value of baseline ¹⁸F-fluorodeoxyglucose (FDG)-PET using PET/CT imaging data from the phase 3 GOYA trial (NCT01287741) of obinutuzumab (G) versus rituximab (R) plus CHOP in patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL).

<figure><img src="image_8.png" /><figcaption>**Figure.** PFS probability over time according to IPI and radiomics feature 'GTSDM AC'.</figcaption></figure>

AC, autocorrelation; GTSDM, grey-tone spatial dependence matrix; IPI, International Prognostic Index; PFS, progression-free survival

**Methods:** GOYA enrolled 1418 pts from 207 centres. Pts were randomized to receive either G (1000 mg) or R (375 mg/m²) every 21 days for 8 cycles, plus CHOP chemotherapy every 21 days for 6-8 cycles. A total of 1334 pts had a baseline FDG-PET scan with detectable lesions. Centrally analysed image data with annotated regions of interest (ROIs) were transferred to the Cuneo imaging core laboratory. The 42 Haralick radiomic image texture features (ITFs) were computed using the PET oncology radiomics test suite (PORTS) for lesions >5 mL. Random Forest analysis for survival data was applied to select the most important clinical, standardised uptake value, and ITF prognostic variables. The selected variables were then inserted into Cox models to predict progression-free survival (PFS).

**Results:** A total of 1085 radiomics-evaluable pts with 9307 lesions were analysed. Random Forest analysis identified the following important variables: International Prognostic Index (IPI), cell-of-origin (COO), Ann Arbor stage, age, bone marrow involvement, total metabolic tumour volume (TMTV), and several ITFs (histogram skewness and energy, grey-tone spatial dependence matrix entropy, correlation, autocorrelation [AC], difference entropy, cluster shade, and low grey-level zone length matrix [GLZSM] emphasis). The accuracy of the Cox model for predicting PFS during a follow-up of 75 months was 0.61 with clinical variables only, 0.62 with the addition of TMTV, and 0.67 with the addition of ITFs. On multivariate analysis, statistically significant variables were IPI ≥3 (hazard ratio [HR] 1.6, p=0.004), non-germinal centre B-cell COO (HR 1.5, p=0.004), >median TMTV (HR 1.2, p=0.0004), AC ≥1100 (HR 1.7, p<0.001), difference entropy (HR 1.3, p=0.03), and GLZSM emphasis (HR 0.6, p=0.03). The radiomics AC feature shows improved

<footnote n="1">¹Medical Physics Division, Santa Croce e Carle Hospital, Cuneo, Italy;
²Department of Radiology, University of Washington, Seattle, WA, United States;
³Department of Oncology and Haematology, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy;
⁴Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy;
⁵Medical Oncology, University of British Columbia, Vancouver, Canada;
⁶¹st Department of Medicine - Department of Haematology, Charles University General Hospital, Prague, Czech Republic;
⁷Product Development Oncology, F. Hoffmann-La Roche Ltd., Basel, Switzerland;
⁸Product Development Oncology, Genentech, Inc., South San Francisco, United States;
⁹Clinical and Biological Sciences, University of Turin, Turin, Italy;
¹⁰Department of Radiology, Icahn School of Medicine, New York, United States</footnote>
discrimination of PFS probability compared to IPI risk category (Figure). Preliminary analyses suggest that several ITF variables, e.g. AC, identified different 3-year PFS for pts treated with R-CHOP (51%, 95% confidence interval [CI] 33%-79%) versus those treated with G-CHOP (79%, 95% CI 68%-92%).

**Conclusions:** A prediction model based on quantitative image texture analysis by radiomics signatures increased the prognostic value of risk prediction of DLBCL patients at baseline. Further analyses with different algorithms are underway to improve the predictive value of radiomics and to develop an effective nomogram to stratify DLBCL pts by risk prior to first-line treatment.

**Acknowledgements:** Supported by a research grant from F. Hoffmann-La Roche Ltd. Third-party editorial assistance, under the direction of Stephane Chauvie, was provided by Helen Cathro of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.

**Keywords:** diffuse large B-cell lymphoma (DLBCL); positron emission tomography (PET); prognostic indices.

**Disclosures:** Chauvie, S: Stock Ownership: Dixit srl; Research Funding: Roche, Fondazione CRC, AIRC. Dalmasso, F: Employment Leadership Position: ISEE srl. Pierce, L: Employment Leadership Position: Precision Sensing LLC; Stock Ownership: Owner of Precision Sensing LLC. Vitolo, U: Consultant Advisory Role: Janssen, Celgene, Roche; Research Funding: Celgene, Roche; Other Remuneration: Speakers' Bureau: Roche, Celgene, Takeda, Gilead, Servier, Sandoz, Janssen; Other: Roche, Janssen, Celgene, Gilead. Martelli, M: Consultant Advisory Role: Roche, Gilead, Novartis, Servier, Sandoz, Janssen, Celgene; Other Remuneration: Speakers' Bureau: Roche, Gilead, Servier, Sandoz, Janssen, Celgene; Other: Roche (ASH). Sehn, L: Consultant Advisory Role: Abbvie, Amgen, Roche, Genentech, Apobiologix, AstraZeneca, Acerta, Celgene, Gilead, Janssen, Kite, Karyopharm, Lundbeck, Merck, MorphoSys, Seattle Genetics, Teva, Takeda, TG Therapeutics; Honoraria: Abbvie, Amgen, Roche, Genentech, Apobiologix, AstraZeneca, Acerta, Celgene, Gilead, Janssen, Kite, Karyopharm, Lundbeck, Merck, MorphoSys, Seattle Genetics, Teva, Takeda, TG Therapeutics; Research Funding: Roche, Genentech. Trněný, M: Consultant Advisory Role: Takeda, Bristol-Myers Squibb, Incyte, Abbvie, Amgen, Roche, Gilead Sciences, Janssen, Celgene, MorphoSys; Honoraria: Janssen, Gilead Sciences, Takeda, Bristol-Myers Squibb, Amgen, Abbvie, Roche, MorphoSys, Incyte; Other Remuneration: Expenses: Gilead Sciences, Takeda, Bristol-Myers Squibb, Roche, Janssen, Abbvie. Nielsen, T: Employment Leadership Position: Roche; Stock Ownership: Roche. Sahin, D: Employment Leadership Position: Roche; Stock Ownership: Roche. Lee, C: Employment Leadership Position: Roche; Stock Ownership: Roche. Mattiello, F: Employment Leadership Position: Roche. Kinahan, P: Consultant Advisory Role: Roche; Stock Ownership: PET/X LLC; Research Funding: GE healthcare; Other Remuneration: University of Washington.

022
PROGNOSTIC VALUE OF PRE-TREATMENT
PET SCAN IN PATIENTS WITH FOLLICULAR
LYMPHOMA RECEIVING FRONTLINE
THERAPY

P. Strati¹ | M. Ahmed¹ | N. Fowler¹ |

F. Hagemeister¹ | L. Fayad¹ | M. Rodriguez¹ |

F. Samaniego¹ | M. Wang¹ | J.R. Westin¹ |

J. Romaguera¹ | M. Noorani¹ | K. Phansalkar¹ |

C. Cheah¹ | L. Feng² | R.E. Davis¹ | L. Nastoupil¹ |

S.S. Neelapu¹

¹Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, United States; ²Biostatistics, MD Anderson Cancer Center, Houston, United States

**Background:** Positron emission tomography (PET) is recommended in follicular lymphoma (FL) for initial staging, evaluation of potential transformation, and response assessment. The prognostic value of pre-treatment PET scan in previously untreated FL patients has not been adequately explored.

**Methods:** We performed a single-institution retrospective analysis of patients with advanced stage low grade FL, without histological evidence of transformation, treated with frontline rituximab-based therapy at MD Anderson Cancer Center between 08/2001 and 04/2014, and analyzed the prognostic significance of maximum standardized uptake value (SUVmax) calculated from pre-treatment PET scan.

**Results:** Three-hundred and forty-six patients were included in the study and median pre-treatment SUVmax was 11 (range, 1.5-42). Among multiple single unit increments of SUVmax, a value of >18 (observed in 52 [15%] patients) showed the strongest association with progression-free survival (PFS)(hazard ratio [HR] 1.5, 95% confidence interval (CI) 0.95-2.3, p=0.08), and was selected as cut-off for further analysis. On univariate analysis, factors associated with SUVmax > 18 were male sex (67% vs 52%, p=0.05), elevated β2-microglobulin (65% vs 47%, p=0.02), elevated LDH (37% vs 13%, p<0.001), presence of B symptoms (35% vs 14%, p=0.01), and largest lymph node ≥ 6 cm (64% vs 30%, p<0.001). On multivariate analysis, largest lymph node ≥ 6 cm was the only factor maintaining its association with SUVmax > 18 (odds ratio [OR] 2.7, 95% CI 1.3-5.3, p=0.006). One-hundred and fifty-one (44%) patients were treated with frontline R-CHOP, and 195 (56%) with other therapies, including BR in 55 (16%) patients, R2 in 63 (18%), RFND in 24 (7%), and single agent rituximab in 53 (15%) patients. Two-hundred and thirty-two (65%) patients received maintenance rituximab and 114 (33%) were observed after completion of frontline therapy. While no differences in use of maintenance therapy were observed between the 2 groups (75% vs 67%, p=0.20), a significantly higher proportion of patients with baseline pre-treatment SUVmax 18 was treated with R-CHOP (75% vs 38%, p<0.001). SUVmax > 18 significantly associated with a lower CR rate among patients treated with non-R-CHOP regimens (45% vs 92%)(p<0.001) but not among patients treated with R-CHOP (p=1). SUVmax > 18 associated with significantly shorter PFS among patients treated with non-R-CHOP regimens (77 months vs not reached, p=0.02), but not among patients treated with R-CHOP (p=0.73) (Figure). SUVmax > 18 associated with shorter overall survival (OS) both in patients
<figure><img src="image_9.png" /></figure>

<figure><img src="image_10.png" /></figure>

treated with R-CHOP (15 year OS 70% vs 75%, p=0.02) and non-R-CHOP regimens (15 year OS 50% vs 75%, p=0.001) (Figure).

**Conclusions:** In conclusion, pre-treatment SUVmax has prognostic value in patients with advanced stage FL receiving rituximab-based therapies, as it may suggest undiagnosed transformation and/or a more aggressive biology. Evaluation in prospective studies is needed to further confirm these findings.

**Keywords:** follicular lymphoma (FL); positron emission tomography (PET); R-CHOP.

## FOCUS ON... SESSION: PEDIATRIC LYMPHOMA

### 023
NON-HODGKIN LYMPHOMA IN ADOLESCENT AND YOUNG ADULTS - A NATIONAL PROSPECTIVE POPULATION-BASED STUDY

R. Carr<fnref n="1" /> | J. Fidalgo<fnref n="1" /> | H. Moller<fnref n="2" />

**Introduction:** Non-Hodgkin Lymphoma (NHL) is common but poorly understood in adolescents and young adults (AYA). English Cancer Registry records of NHL diagnosed 2008 to 2013 found patients aged 15-23y had 2y survivals, including all NHL types, 10% lower than younger children and 7% less than adults aged 24-30y. Inferior survival was most marked for diffuse large B-cell lymphoma (DLBCL) and

Burkitt's lymphoma (BL). The reasons for these poor outcomes are unclear, particularly as AYA with NHL are infrequently recruited into clinical trials. The study purpose is to document the frequency of NHL subtypes, treatments and outcomes in AYA aged 15y to 29y, diagnosed in England and Wales during 4 years, January 2015 to December 2018, to understand the reasons for treatment failure.

**Methods:** The study records patient demographic and clinical data from two sources to create 2 separate, but overlapping cohorts. Cohort 1 is a whole population cohort based on information in the English Cancer Registry which includes patient demographics, diagnosis, where treated and updated vital status. It does not record treatment or response. Cohort 2 comprises consented patients treated at regional cancer centres in England and Wales. This cohort has record of diagnosis detail, staging, all treatments, response, survival to 2y from diagnosis, and notified of mortality to 5y.

**Results:** Cohort 1 shows an annual incidence of 250 new cases of NHL diagnosed in AYA annually, with approximately 125 cases aged 15-24y and 125 aged 25-29y. The most frequent population-based diagnoses being proportionally: DLBCL 38%, BL 15%, Primary Mediastinal NHL 8%, Follicular NHL 7%. We report here mortality rates for the 265 consented patients (cohort 2) with reported outcomes and median follow up of 24 months. There are 167 patients aged 15-24y and 98 patients 25-29y. Overall 14% have died. The highest mortality, in order of frequency: Hepato-splenic T-cell NHL 4/4 (100%), Peripheral T-cell 2/3 (66%), T-Lymphoblastic 4/7 (57%), BL 11/34 (32%), non-GC DLBCL 10/64 (16%), Alk+ ALCL 2/17 (12%), post-transplant LPD 2/17 (12%). Mortality is greater in the 25-29y patient group, but early death more frequent in 15-24y olds; 7 patients are recorded as dying within 24h of hospital admission.

**Conclusions:** This preliminary analysis highlights the poor prognosis of T-cell NHL at this age. More surprising is the 32% deaths in Burkitt's

<footnote n="1">¹Haematology, Guy's & St Thomas' Hospital, London, United Kingdom;</footnote>

<footnote n="2">²Cancer Epidemiology, King's College London, London, United Kingdom</footnote>