End of Treatment Peripheral Blood TCR
Evaluation for Minimal Residual Disease
Evaluation in Peripheral T-cell Lymphomas
Neha Mehta-Shah, MD, MSCI1 , Todd A Fehniger, MD, PhD1 , Eric D Jacobsen, MD2 , Katrina Peterson1 , Brad S. Kahl, MD1 , Nancy L. Bartlett, MD1,Amanda F Cashen, MD1 , Armin Ghobadi, MD1 , Anne Fischer, BS1 , Beth Reagan1 , Alison J. Moskowitz, MD3 , Fei Wan1 , Natalie Hill4 , Ying Huang, PhD4 ,Kasey Hutt, PhD4 , Edgar Vigil4 , Meredith Olson4 , Austin Jacobsen4 and Steven M. Horwitz, MD3
1 Washington University in St. Louis, St. Louis, MO; 2 Dana Farber Cancer Institute, Boston, MA;
3 Memorial Sloan Kettering Cancer Center, New York, NY; 4 Invivoscribe, San Diego, CA

Disclosures• Mehta-Shah: Institutional research funding from: Bristol Myers-Squibb, Celgene, Verastem, Corvus, Genetech/Roche, Innate. Consultancy for
Kyowa Hakko Kirin, C4 Therapeutics, Daiichi Sankyo, Karyopharm, Ono : Consultancy• Fehniger: Research funding from: HCW Biologics, Compass Therapeutics, ImmunityBio. Consultancy for Indapta, Nkarta, Kiadis, Orca,Biosystems, Wugen.
• Jacobsen: Research funding from Novartis, Pharmacyclics, F. Hoffmann-LaRoche, Consultancy from: Acerta, Astra-Zeneca, Merck; Honoraria fromTakeda• Kahl: Research Funding from ADC Therapeutics, Acerta, Beigene. Consultancy for AstraZeneca Pharmaceuticals LP, AbbVie, BeiGene, Acerta,Janssen, Celgene, Genentech, Roche, Pharmacyclics, ADC Therapeutics. Membership on an entity's Board of Directors or advisory committees for
AstraZeneca, ADC therapeutics, Janssen and BeiGene.
• Bartlett: Research funding from Seattle Genetics, Millennium, Merck, Affimed, Acerta, Janssen, Autolous, Roche/Genenetch, BMS/Celgene, ,Pharmacyclics, Immune Design, Kite, Forty Seven, : Consultancy for Seattle Genetics, BTG, ADC Therapeutics, Pfizer, WuGen, EUSA,Roche/Genentech, Bristol Myers Squibb, Kit, Membership on an entity's Board of Directors or advisory committees for Seattle Genetics, Pfizer• Ghobadi: Research funding from Amgen, Kite, Consultancy from Amgen, WuGen, EUSA, Bristol Myers Squibb, Kite
• Moskowitz: Research Funding from Merck, Incyte, Seattle Genetics, Bristol-Myers Squibb; Consultancy form Seattle Genetics, ImbriumTherapeutics, L.P, Miragen Therapeutics; Incyte; Merck:• Huang, Hutt, Vigil, A Jacobsen, Olson: Employed by Invivoscribe• Horwitz: Research Funding from Daiichi Sankyo, Corvus, Portola, Trillium, Seattle Genetics, Millenium/Takeda, Infinity, Verastem, Aileron, ADCTTherapeutics, Celgene, Forty Seven, Kiowa Hakka Kirin, Consultancy from: GlaxoSmithKline, Myeloid Therapeutics, Innate Pharm.,
Mundipharma, Beigene, Portola, Corvus, Trillium, Seattle Genetics, Millenium/Takeda, Kyowa Hakka Kirin, Forty Seven, Celgene, Aileron; ADCTTherapeutics, ASTEX, Affirmed, Miragen, Kura Oncology; Janssen; Vividion Therapeutics; Verastem, C4 Therapeutics

Background••

Peripheral T-cell lymphomas are a rare subtype of non-Hodgkin lymphomaHigh rate of relapse to standard therapy:– 80% overall response rate to anthracyline based chemotherapy
Outcomes By Intent to Consolidated– 5 year PFS approximately 20% for most subtypes•

with Auto-HSCT
in Swedish Registry

Autologous transplant is considered in first remission– Benefits approximately 20% of patients•Auto-SCT(n = 128)

No AutoSCT(n = 124)

5 yr OS

48%

26%– To evaluate who is at highest risk of relapse
5 yr PFS– Who most benefits from a consolidative autologous transplant

41%

20%

Allogeneic transplant can be curative– Median survival from relapsed/refractory disease is
6-10 months•

Biomarkers would be critical:

Ellin et al Blood 2014

•Background

Minimal residual disease markers are being
studied to:– Predict relapse– Determine who benefits from maintenance orconsolidative therapy– Promote early discontinuation of therapy•T-cell receptor gene rearrangement (TCR) by
next generation sequencing is able to detect aknown TCR clonotype at 10-5
• Highly specific and sensitive• Lends itself towards MRD evaluation in T-celllymphomas

Courtesy of Maria Arcila (MSKCC)

Shah et al AMP 2017

•Methods
Hypothesis:••

Primary Objective:••

To estimate the percentage of patients with a dominant tumor sequence identified from the pretreatment tumor specimen.

Secondary Objectives••••

Next generation sequencing based TCR clonality assays is a feasible method of evaluating minimalresidual disease

To study whether a novel NGS-based TCR clonality assay to evaluate MRD (LymphoTrack) can
prognosticate risk of relapse in PTCL, predict response to treatment
To evaluate whether the rate of decline of the tumor specific sequence or sequences predict duration ofresponse.
To characterize the lead time from MRD positivity to subsequent clinical relapse.

Exploratory Objective•

To explore the ability of cfDNA sequencing analysis to assess MRD in PTCL.

Study Design

A prospective, multi-institutional, non-therapeutic cohort study
Eligibility:- Untreated PTCL-NOS,AITL, ALK- ALCL, ALK+
ALCL, MEITL, EATL
- Pretreatment sample toevaluate tumor TCR
sequence
Exclusion:- CTCL, NK/T-cell, ATLL,HSPTCL

NCT03297697

Statistical Design•

Aim to demonstrate feasibility of evaluating for MRD by TCR clonotype(Lymphotrack) in peripheral blood at baseline– Feasibility: if TCR clonotype positive at baseline in >60% of cases•Powered to detect 35% difference in 2 year PFS between those who havenegative vs. positive peripheral blood MRD evaluation at end of treatment– 2 year PFS for End of Treatment PET– Negative: 60%, Positive 25%•Sample size: 42 patients.
– A one-sided log rank test with type I error of 0.1 will have power of 0.9 to detect a 35%
difference in 2-year PFS

Patient Characteristics
Histology

N (%)

Therapy

N (%)

PTCL

16 (42%)CHOP

3 ( 16%)AITL

10 (26%)CHOEP

10 (52%)

ALCL, ALK-

7 (18%)

BV-CHP

4 (21%)

ALCL, ALK+

5 (13%)CEOP

1 (5%)MEITL

1 (3%)

CHOP+ azacitidine

1 (5%)

Autologous Transplant

7 (37%)

Response to Therapy
AgeMedian (Range)

61 (22-80)

CR

13 (68%)PR

1 (5%)

PD

5 (26%)• 38 patientsenrolled• 19 completed
therapy and had
end of treatment
TCR available
for analysis

Results

End of Treatment
Blood

Baseline
Blood

Baseline Tumor Tissue
15 (78.9%) TCR clonotype +PET/CT CR (n=10)
8 (80%) TCR clonotype +2 (20%) TCR clonotype –At Median follow up
13.1 mo, 1 patient
has relapsed

4 (21.1%) TCR clonotype –• 3 PTCL NOS, 1 ALK+ ALCLPET/CT PR/PD (n=5)
5(100%) TCR clonotype +End of Treatment Blood• 13/15 (86.7%) TCR clonotype +• 2/15 (13.3%) TCR clonotype –•Conclusions

Measurement of peripheral blood TCR at the end oftreatment is feasible in PTCL using next generation sequencing with a known
tumor clonotype.

••

Lack of radiographic CR was highly correlated with detectable TCR,Detectable TCR was also frequently seen in complete remission by PET/CT.

•Longer follow up is required to:– Determine if peripheral blood TCR clonotype at the end of CHOP-based therapy
predicts likelihood of relapse– Evaluate the dynamics of TCR clonotype during and after completion oftreatment– Evaluate if ASCT changes presence of minimal residual diseaseAcknowledgements

Washington University in St. Louis• Brad Kahl
• Todd Fehniger• Nancy Bartlett• Amanda Cashen• Armin Ghobadi• Obi and Malachi Griffith
MSKCC• Steven Horwitz
DFCI• Eric Jacobsen

Research Team:• Anne Fischer• Katrina Peterson• Stephanie Myles• Kim Trinkaus and Andy Ni
Funding Sources• Lymphoma ResearchFoundation• T-cell Leukemia LymphomaFoundation• Invivoscribe• Paul Calabresi K12 Award