-Author name in bold denotes the presenting author
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602 TRANSCEND FL: Phase 2 Study Primary Analysis of Lisocabtagene Maraleucel as Second-Line Therapy in Patients with High-Risk Relapsed or Refractory Follicular LymphomaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Immunotherapy
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Lymphomas, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, indolent lymphoma, Therapies, Lymphoid Malignancies
Sunday, December 10, 2023: 4:45 PM

Franck Morschhauser, phd1, Saurabh Dahiya2*, Maria Lia Palomba, MD3, Alejandro Martin Garcia-Sancho, MD4*, Juan Luis Reguera, MD5,6*, John Kuruvilla, MD, FRCPC7, Ulrich Jaeger, MD8*, Guillaume Cartron, MD, Ph-D9*, Koji Izutsu, MD, PhD10, Martin Dreyling, MD11, Brad S. Kahl, MD12, Herve Ghesquieres, MD13*, Kirit Ardeshna, MD, MA, FRCP14*, Hideki Goto, MD, PhD15*, Anna Maria Barbui, MD16*, Jeremy S. Abramson, MD17, Peter Borchmann, MD18, Isabelle Fleury, MD19, Stephan Mielke, MD20, Alan Skarbnik, MD21,22, Sven de Vos, MD, PhD23*, Manali Kamdar, MD24*, Reem Karmali, MD, MSc25, Andreas Viardot, MD PhD26, Thalia Farazi27, Omotayo Fasan28, James Lymp, PhD29*, Min Vedal, PhD29*, Rina Nishii, PhD28*, Ariel Avilion, PhD29*, Jessica Papuga, PhD30* and Loretta J. Nastoupil, MD31

1CHU de Lille, Lille, France
2Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Palo Alto, CA
3Memorial Sloan Kettering Cancer Center, New York, NY
4Department of Hematology, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain
5University Hospital Virgen del Rocío, Sevilla, Spain
6Instituto de Biomedicina de Sevilla (IBIS), Servicio de Hematología, Hospital Universitario Virgen del Rocío and Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Sevilla, Sevilla, Spain
7Princess Margaret Cancer Centre, Toronto, ON, Canada
8Medical University of Vienna, Vienna, Austria
9Clinical Hematology Department, Montpellier University Hospital Center, Montpellier, France
10National Cancer Center Hospital, Tokyo, Japan
11Medizinische Klinik III, Klinikum der Universität, LMU München, Munich, Germany
12Washington University School of Medicine in St. Louis, St. Louis, MO
13Hôpital Lyon Sud, Lyon, France
14University College London Hospitals NHS Foundation Trust - University College Hospital, London, United Kingdom
15Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
16Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
17Massachusetts General Hospital Cancer Center, Boston, MA
18Universität zu Köln, Köln, Germany
19Hôpital Maisonneuve – Rosemont, Montreal, QC, Canada
20Karolinska Institutet and University Hospital, Karolinska Comprehensive Cancer Center, Stockholm, Sweden
21Novant Health Cancer Institute, Lymphoma and CLL Program, Charlotte, NC
22Novant Health Cancer Institute, Charlotte, NC
23UCLA Santa Monica Medical Centre, Santa Monica, CA
24University of Colorado Cancer Center, Aurora, CO
25Northwestern University Feinberg School of Medicine, Chicago, IL
26Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
27Bristol Myers Squibb, San Francisco, CA
28Bristol Myers Squibb, Princeton, NJ
29Bristol Myers Squibb, Seattle, WA
30Bristol Myers Squibb, Boudry, Switzerland
31The University of Texas MD Anderson Cancer Center, Houston, TX

Background: Results with CD19-directed CAR T cell therapy in patients (pts) with second-line (2L) R/R follicular lymphoma (FL) and high-risk features, such as progression of disease within 24 months (POD24) from diagnosis or double refractory to anti-CD20 antibody plus alkylator, have not been previously reported. TRANSCEND FL (NCT04245839), a global, phase 2, open-label, single-arm, multicohort, pivotal study, assessed efficacy and safety of the anti-CD19 CAR T cell therapy lisocabtagene maraleucel (liso-cel) in pts with second line or later (2L+) R/R indolent NHL. Some data from the primary analysis were previously reported, including safety in 2L+ R/R FL, and focused on efficacy in third line or later R/R FL (Morschhauser F, et al. Hematol Oncol 2023;41[S2]:877‒880). Here, we report primary analysis results in the cohort of pts with 2L high-risk R/R FL.

Methods: Eligible pts in the 2L R/R FL cohort had biopsy-confirmed FL before enrollment and must have had POD24 with treatment ≤ 6 months from original FL diagnosis and/or must have had high tumor burden as defined by modified Groupe d’Etude des Lymphomes Folliculaires (mGELF) criteria. All pts received 1 prior combination systemic therapy with an anti-CD20 antibody and alkylator. Eligible pts received liso-cel (100 × 106 CAR+ T cells) after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed with reconfirmation of PET-positive disease before LDC. The primary endpoint was ORR per independent review committee (IRC) by PET/CT using Lugano 2014 criteria. Secondary endpoints included CR rate, duration of response (DOR), PFS, OS, safety, and cellular kinetics. Pharmacodynamic endpoints were exploratory.

Results: At data cutoff (January 27, 2023), 23 of 25 leukapheresed pts received liso-cel and were evaluable for safety and efficacy per IRC; 1 received nonconforming product and 1 reached CR after bridging therapy and no longer met eligibility criteria. Median (range) age was 53 y (34–69), 74% had stage III/IV disease, and 35% were high-risk per FL International Prognostic Index (FLIPI). Sixty-five percent of pts had POD24 from initiation of first-line combination chemoimmunotherapy (52% had POD24 from diagnosis), 70% met mGELF criteria (mGELF only, 48%; mGELF and POD24 from diagnosis, 22%), and 48% were double refractory to anti-CD20 antibody plus alkylator. Median (range) on-study follow-up was 18.1 months (1.0–26.8). In efficacy-evaluable pts, the ORR and CR rate were both 95.7% (95% CI, 78.1–99.9; 1-sided P < 0.0001; Table).

With a median follow-up of 16.8 months and 17.8 months, respectively, median DOR and PFS were not reached; 12-month DOR and PFS were 89.8% and 91.3%, respectively. The most common grade (gr) ≥ 3 treatment-emergent AEs (TEAE) were cytopenias; neutropenia was most frequent (52%). Cytokine release syndrome (CRS) occurred in 12 (52%) pts (no gr ≥ 3). Median (range) time to onset and resolution of CRS was 6 days (2–9) and 3 days (2–7), respectively. Neurological events (NE) occurred in 4 (17%) pts, with 1 (4%) gr 3 and no gr 4–5 (Table). Median (range) time to onset and resolution of NEs was 8.5 days (6–11) and 2.5 days (1–4), respectively. Three (13%) pts received tocilizumab/steroids for CRS/NEs. Prolonged cytopenia (gr ≥ 3 laboratory values at Day 29) occurred in 3 (13%) pts; all recovered to gr ≤ 2 by Day 90. No gr ≥ 3 infections were reported. One TEAE death occurred in the context of IRC-assessed disease progression due to gr 5 macrophage activation syndrome (MAS). Liso-cel showed rapid expansion with median (range) time to maximum transgene levels of 10 days (7–11). Persistence of liso-cel transgene was detected up to Month 12 in 5 of 18 (28%) pts. B-cell aplasia (< 3% CD19+ B cells in peripheral blood lymphocytes) after liso-cel infusion was rapid and maintained in ≥ 95% of pts through Month 2.

Conclusions: This is the first report of outcomes in 2L high-risk R/R FL with CD19-directed CAR T cell therapy. In this population, liso-cel achieved very high CR rates (22 of 23 pts); deep and durable remissions, with follow-up ongoing; and a favorable safety profile with low rates of severe (gr ≥ 3) CRS, NEs, and prolonged cytopenia, and no severe infections. These data support liso-cel as a potential new treatment option in pts with 2L R/R FL at high-risk for treatment failure.

Disclosures: Morschhauser: Janssen: Honoraria; Gilead: Consultancy, Other: Advisory Board; BMS: Consultancy, Other: Advisory Board; AbbVie: Consultancy, Other: Advisory Board; Celgene: Other: Advisory Board; Novartis: Consultancy, Other: Advisory Board; Incyte: Other: Advisory Board; Epizyme: Other: Advisory Board; Genmab: Consultancy, Other: Advisory Board; Roche: Consultancy, Honoraria, Other: Advisory Board. Dahiya: Adaptive Biotechnologies: Consultancy; Bristol Myers Squibb: Consultancy; Incyte: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Palomba: Rheos: Honoraria; Seres Therapeutics: Honoraria, Patents & Royalties; Smart Immune: Honoraria; Thymofox: Honoraria; Ceramedix: Honoraria; BMS: Honoraria; Juno: Honoraria, Patents & Royalties; Cellectar: Honoraria; Novartis: Honoraria; MustangBio: Honoraria; Pluto Immunotherapeutics: Honoraria; Kite: Honoraria; GarudaTherapeutics: Honoraria; Synthekine: Honoraria. Martin Garcia-Sancho: Kyowa Kirin: Consultancy, Honoraria; Clinigen: Consultancy; Eusa Pharma: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead / Kite: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; ADC Therapeutics America: Consultancy, Honoraria; Miltenyi: Consultancy, Honoraria; Ideogen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd, BMS / Celgene, Kyowa Kirin, Novartis, Gilead / Kite, Incyte, Lilly, ADC Therapeutics America, Miltenyi, Ideogen, Abbvie, Sobi: Consultancy; F. Hoffmann-La Roche Ltd, BMS/Celgene, Janssen, Gilead/Kite, Takeda, Eusa Pharma, Abbvie: Honoraria; Roche: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Reguera: BMS: Speakers Bureau; KITE: Speakers Bureau; AMGEN: Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Kuruvilla: Abbvie, BMS, Gilead, Merck, Roche, Seattle Genetics: Consultancy; Abbvie, Amgen, Astra Zeneca, BMS, Genmab, Gilead, Incyte, Janssen, Merck, Novartis, Pfizer, Roche, Seattle Genetics: Honoraria; Roche, Astra Zeneca, Merck: Research Funding; Karyopharm: Other: DSMB. Jaeger: Innovative Medicines Initiative 2 Joint Undertaking: Research Funding; BMS, Novartis, Gilead, Miltenyi, Janssen and Roche: Honoraria. Cartron: MabQi: Consultancy; MedxCell: Consultancy; Janssen: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Emercell: Consultancy; BMS: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Jansen, Gilead, Novartis, F. Hoffmann-La Roche Ltd, BMS, Abbvie: Honoraria; MedxCell, Ownards Therapeutics, MabQi, Emercell, F. Hoffmann-La Roche Ltd, BMS, Abbvie: Consultancy; MabQi, Ownards Therapeutics, Abbvie, Roche, Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Ownards Therapeutics: Consultancy; Roche: Consultancy, Honoraria. Izutsu: Nihon Kayaku: Honoraria; Meiji Seika: Honoraria; Eli Lilly: Honoraria; SymBio Pharmaceuticals: Honoraria; Janssen: Honoraria; Regeneron: Research Funding; Loxo Oncology: Research Funding; Beigene: Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Yakult: Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Incyte: Research Funding; Astellas Amgen: Research Funding; Nippon Shinyaku: Consultancy; Mitsubishi Tanabe Pharma: Consultancy; Zenyaku Kogyo: Consultancy; Kyowa Kirin: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Genmab: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Ono Pharmaceuticals: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Eisai: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding. Dreyling: Astra Zeneca, Beigene, Gilead/Kite, Janssen, Lilly, Novartis, Roche: Honoraria; Abbvie, Bayer, BMS/Celgene, Gilead/Kite, Janssen, Roche: Research Funding; Abbvie, Astra Zeneca, Beigene, BMS/Celgene, Gilead/Kite, Janssen, Lilly/Loxo, Novartis, Roche: Other: Scientific advisory boards. Ghesquieres: Gilead, Roche, BMS, Abbvie: Honoraria; Gilead, Roche: Consultancy. Ardeshna: Novartis, Gilead, Bristol Myers Squibb: Other: travel support. Goto: SymBio: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Honoraria; Chugai: Honoraria; Kyowa Kirin: Honoraria, Research Funding. Abramson: Century Therapeutics: Consultancy; Epizyme: Consultancy; Genentech: Consultancy; Genmab: Consultancy; Incyte: Consultancy; Interius: Consultancy; Janssen: Consultancy, Honoraria; Kite Pharma: Consultancy; Kymera: Consultancy; Lilly: Consultancy; Merck: Research Funding; MorphoSys: Consultancy; Mustang Bio: Consultancy, Research Funding; Ono Pharma: Consultancy; Regeneron: Consultancy, Honoraria; Seagen Inc.: Research Funding; Takeda: Consultancy; Celgene: Consultancy; Novartis: Consultancy; EMD Serono: Consultancy; Cellectar Biosciences: Consultancy; Alimera Sciences: Consultancy; Karyopharm Therapeutics: Consultancy; C4 Therapeutics: Consultancy; Bluebird Bio: Consultancy; AI Therapeutics: Research Funding; Caribou Biosciences: Consultancy; BMS: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy. Borchmann: BMS Germany; MSD Oncology: Honoraria; MSD Oncology; Takeda: Research Funding. Fleury: Abbvie, Astrazeneca, Beigene, Janssen, Roche: Consultancy; Abbvie, Astrazeneca, Bristol Myers Squibb, Gilead, Janssen, Merck, Novartis, Roche, Seattle Genetics: Consultancy, Other: Advisory board; BMS: Consultancy; Incyte, Gilead, Novartis, Seagen: Consultancy, Speakers Bureau. Mielke: SWECARNET: Other: Founder/Leadership (via my institution) ; ScientifyResearch: Other: Founder (spouse) ; Immunicum/Mendes, Miltenyi: Other: Participation on a Data Safety Monitoring Board or Advisory Board; Celgene/BMS, Novartis, Janssen, Gilead/KITE, JSMO, Pfizer: Speakers Bureau. Skarbnik: Abbvie: Consultancy, Honoraria, Speakers Bureau; Alexion: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Speakers Bureau; Genmab: Consultancy, Honoraria, Speakers Bureau; Epizyme: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Lilly: Consultancy, Honoraria, Speakers Bureau; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; SeaGen: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Beigene: Honoraria, Speakers Bureau; ADC therapeutics: Honoraria, Speakers Bureau. de Vos: BeiGene: Consultancy. Kamdar: Adaptive Biotechnologies: Consultancy; Celgene/ Bristol-Myers Squibb: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy; Novartis: Research Funding; syncopation: Consultancy; Genentech: Consultancy; Beigene: Consultancy; ADC therapeutics: Consultancy; caribou biosciences: Consultancy; SeaGen: Speakers Bureau; Celgene: Other: DMC; Genentech: Other: DMC. Karmali: BMS: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Lilly: Consultancy, Honoraria; Genentech/Roche: Consultancy, Honoraria; Takeda: Research Funding; Calithera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Miltenyi: Consultancy, Honoraria, Research Funding; Morphosys: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy. Viardot: F. Hoffmann-La Roche Ltd, Abbvie, Kite/Gilead, BMS: Consultancy; F. Hoffmann-La Roche Ltd, Abbvie, Kite/Gilead, BMS: Honoraria; BMS: Research Funding. Farazi: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Fasan: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Sanofi Genzyme: Speakers Bureau; Oncopeptides: Other: Advisory Board, Speakers Bureau. Lymp: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Vedal: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Nishii: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Avilion: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Papuga: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Nastoupil: Gilead Sciences/Kite Pharma: Honoraria, Research Funding; AstraZeneca: Honoraria; Regeneron: Honoraria; Genentech, Inc., Genmab, Gilead/Kite, Janssen, Merck, Novartis, Takeda: Honoraria, Research Funding; ADC Therapeutics: Honoraria; DeNovo: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Caribou Biosciences: Honoraria, Research Funding; AbbVie: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding.

*signifies non-member of ASH