Kte-X19 in Relapsed or Refractory Mantle-Cell Lymphoma, a "Real-Life" Study from the Descar-T Registry and Lysa Group
Authors: Herbaux Charles , Bret Caroline , Di Blasi Roberta , Bachy Emmanuel , Beauvais David , Gat Elodie , Gastinne Thomas , Broussais Florence , Cartron Guillaume , Cuffel Alexis , Ysebaert Loic , Roussel Mikael , Bouabdallah Krimo , Guy Julien , Campidelli Arnaud , Van Laethem François , Casasnovas Rene-Olivier , Dulery Remy , Morschhauser Franck , Caillat-Zucman Sophie , Houot Roch , Le Gouill Steven 
Published: November 2021

Abstract
Introduction
The French health agency granted access to KTE-X19 in its early access program (French ATUs) for patients with relapsed or refractory (R/R) mantle-cell lymphoma (MCL) who failed after at least one line of chemoimmunotherapy and Bruton's tyrosine kinase (BTK) inhibitor. DESCAR-T is the French national registry for all patients treated with CAR-T cells (commercial or early access program). DESCAR-T designed and sponsored by LYSA/LYSARC aims to collect "real-life" data about CAR-T cell eligible patients in all hematological malignancies. We report the first results of "real-life" use of KTE-X19 in R/R MCL.
Methods.
All patients with MCL and registered in DESCAR-T were eligible for the present study. The data collection started at time of the medical decision to treat with KTE-X19. All patients gave informed consent before DESCAR-T registration. Response was determined by investigators per the Lugano criteria. CAR-T cells were monitored in peripheral blood samples of 14 patients by multiparametric flow cytometry routine procedures, using the biotinylated CD19 CAR detection reagent (Miltenyi Biotec©).
Results
Our study started at the beginning of the French early access program on January 7 th 2020 until data extraction on June 18 th 2021. A total of 57 patients were registered, including 6 commercial use registrations of KTE-X19 (after the end of early access program). KTE-X19 product has been ordered for 55 patients of whom 47 have been infused with CAR-T cells. KTE-X19 was not ordered in 2 cases because of patient decision. It was not infused in 8 patients because of disease progression (n=3), manufacturing failure (n=3), cardiac disease (n=1) and uncontrolled infection (n=1). At the time of registration in DESCAR-T, median age of infused patients was 67 years (range 45-79), 93.6% of patients were male. Median number of prior lines of treatment was 3 (range 2-8) with 34% of autologous stem cell transplant. Initial Ki67 was high (&gt;30%) in 78.6% of patients, 52.4% of patients had elevated LDH and 21.1% had a poor performance status (PS≥2) at inclusion.Median time between CAR-T order and infusion was 56 days (range 35-134) and 87.2% of patients had a bridging therapy. Median follow-up since CAR-T administration was 3.3 months (range 0-12.6). The best overall response rate for the 42 patients with at least one efficacy evaluation was 88%, including CR in 61.9%. PFS calculated from KTE-X19 infusion at 6 months was 57.9% (Figure A) and median duration of 5.3 months. Cytokine release syndrome (CRS) was observed in 78.7% of patients and a neurotoxicity in 48.9%. Transfer in ICU was needed in 27.7% of patients, with a median duration of hospitalization of 5 days. CRS or neurotoxicity of ≥ grade 3 were seen in 4 patients (8.5%), one patient presented both AEs. Among the 47 infused patients, 5 died, 4 of progressive disease and 1 of grade 5 CRS. Cellular kinetics parameters including area under the curve (AUC) representing the exposure from day 0 to day 28 (Figure B), maximal expansion post infusion (C MAX, Figure C) and time to maximal expansion (T MAX, Figure D) are shown. We observed a statistical trend to a shorter T MAX in responders.
Conclusion
This first analysis of "real-life" use of KTE-X19 supports results of clinical trials using CAR-T cells in R/R MCL. The safety profile and the overall response rate are also in line with previously published data. Taken together, the present "real-life" study experience supports the use of KTE-X19 in R/R MCL who failed after BTKi. Updated results will be presented at the meeting.
Figure 1 Figure 1.

Disclosures
Herbaux: Abbvie: Honoraria, Research Funding; Roche: Honoraria; Janssen: Honoraria; Takeda: Honoraria, Research Funding. Di Blasi: Kite, a Gilead Company: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Ysebaert: Abbvie, AstraZeneca, Janssen, Roche: Other: Advisory Board, Research Funding. Bouabdallah: Abbvie: Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Sandoz: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Dulery: Novartis: Honoraria; Takeda: Consultancy; Gilead: Other: Travel support and registration fees for scientific meetings . Morschhauser: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Janssen: Honoraria; Genentech, Inc.: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees. Houot: MSD: Honoraria; Gilead: Honoraria; Roche: Honoraria; Bristol-Myers Squibb: Honoraria; Kite: Honoraria; Novartis: Honoraria; Jsnssen: Honoraria; CHU Rennes: Current Employment; Celgene: Honoraria.