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3125 Five-Year Survival of Patients (pts) from Transcend NHL 001 (TRANSCEND) Supports Curative Potential of Lisocabtagene Maraleucel (liso-cel) in Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Adult, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Jeremy S. Abramson, MD1, Maria Lia Palomba, MD2, Leo I. Gordon, MD3, Matthew Lunning, DO4, Michael Wang, MD5, Jon E. Arnason, MD6, Manali Kamdar, MD, MBBS7*, David G. Maloney, MD, PhD8, Mazyar Shadman, MD, MPH8*, Charalambos Andreadis, MD, MS9*, Alison R. Sehgal, MD10, Scott R. Solomon, MD11, Nilanjan Ghosh, MD, PhD12, Juliana E. Hidalgo-López, MD13*, Jing Wang, MS, MA14*, Ken Ogasawara, PhD, MPH13*, Ashvin Singh, MBS13* and Tanya Siddiqi, MD, MBBS15*

1Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
2Memorial Sloan Kettering Cancer Center, New York, NY
3Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL
4University of Nebraska Medical Center, Omaha, NE
5The University of Texas MD Anderson Cancer Center, Houston, TX
6Beth Israel Deaconess Medical Center, Boston, MA
7University of Colorado Cancer Center, Aurora, CO
8Fred Hutch Cancer Center, University of Washington, Seattle, WA
9University of California, San Francisco, San Francisco, CA
10University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA
11Northside Hospital Cancer Institute, Atlanta, GA
12Atrium Health, Levine Cancer Institute, Charlotte, NC
13Bristol Myers Squibb, Princeton, NJ
14Bristol Myers Squibb, Seattle, WA
15City of Hope National Medical Center, Duarte, CA

Background: TRANSCEND (NCT02631044) demonstrated high ORR/CR rate with a manageable safety profile in R/R LBCL. At 2-y follow-up, liso-cel showed durable remissions (median duration of response [DOR], 23.1 mo) with no new safety signals (Abramson JS, et al. Blood 2024). In ZUMA-1, axicabtagene ciloleucel (axi-cel) showed a median OS of 25.8 mo with 5-y OS rate of 42.6% and 5-y disease-specific survival (DSS) rate of 51.0% (Neelapu SS, et al. Blood 2023). Here, we present 5-y survival results in the LBCL cohort of TRANSCEND, including data from the long-term follow-up (LTFU; NCT03435796) study.

Methods: Adult pts with R/R LBCL after ≥ 2 prior lines of systemic therapy were eligible. Bridging therapy was allowed and PET-positive disease was reconfirmed before lymphodepletion. Response was evaluated per Lugano 2014 criteria by independent review committee (IRC). Primary endpoints included AE rates and ORR. Liso-cel transgene levels were assessed in peripheral blood by qPCR (lower limit of detection, 5 copies/reaction).

Pts who completed the 2 y of study follow-up or who withdrew early could enroll in a separate LTFU study assessing safety and OS for up to 15 y after liso-cel; however, no IRC response assessments were performed in LTFU.

Results: Demographics and baseline characteristics for pts in the liso-cel–treated set (n = 270) were reported (Abramson JS, et al. Blood 2024). At the final TRANSCEND data cutoff (05/16/2024), 124 (46%) pts had completed the study and 146 (54%) had discontinued; 88 liso-cel–treated pts enrolled to LTFU. Median on-study follow-up (including LTFU) was 20.3 mo (range, 0.2–89.4). Liso‑cel showed high response rates and durable remissions in the efficacy-evaluable set (n = 257) as observed at the 2-y follow-up with ORR of 73% (CR rate, 53%), median DOR of 23.1 mo (95% CI, 8.6–not reached [NR]), and median duration of CR of 26.1 mo (95% CI, 23.1–NR). Median PFS was 6.8 mo (95% CI, 3.3–12.7).

Median OS was 27.5 mo (95% CI, 16.2–47.3). Estimated 5-y OS rate was 38.1% (95% CI, 31.6%–44.7%). Six pts enrolled in the LTFU study were followed and alive at 7 y after infusion. Pts who achieved CR had prolonged OS (median [95% CI], NR [53.9–NR]) with 5-y OS rate of 55.9% (95% CI, 45.8%–64.9%). Estimated 5-y DSS rate (excluding deaths unrelated to disease progression) was 52.0% (95% CI, 45.1%–58.5%). Among the 345 leukapheresed pts, 175 (51%) died after CAR T cell infusion, with 136 (39%) deaths occurring > 90 d after infusion, most commonly due to PD (n = 102; 30%). Thirty pts died > 2 y after CAR T cell infusion, including 10 due to PD, 2 due to AEs (progressive multifocal leukoencephalopathy [PML] and COVID-19 pneumonia as noted below as grade 5 infections), 8 due to unknown reasons, and 10 due to other reasons, suggesting that most deaths occurred before 2 y and that pts who were alive at 2 y had increased chances of prolonged survival. Liso‑cel was present in peripheral blood in 34% (13/38) of pts with samples available at 5 y after infusion.

Among the 249 pts with data in the post-TE period (≥ 91 d after liso-cel infusion or initiation of another anticancer therapy or liso-cel retreatment), no new safety signals were observed; 45% of pts had any-grade AEs and 25% had grade ≥ 3 AEs. The most common grade ≥ 3 post-TE AEs were cytopenias (neutropenia, 7%; anemia, 6%; thrombocytopenia, 4%). Median (range) duration of grade 3–4 prolonged (ie, unresolved at D29 visit) neutropenia, anemia, and thrombocytopenia was 26.5 d (3–337), 22.0 d (4–73), and 30.5 d (2–329), respectively. In the post-TE period, 14 (6%) pts had grade ≥ 3 infections (grade 5, n = 3). Of the 3 pts with grade 5 infections, 2 had received subsequent anticancer therapy; 1 died of septic shock on D79 after infusion and 5 d after subsequent anticancer therapy, 1 died of PML on D775 after infusion, and 1 died of COVID-19 pneumonia on D1660 after infusion and after subsequent anticancer therapy on D135. Nineteen (8%) pts had second primary malignancies (most commonly nonmelanoma skin cancers [n = 7] and myelodysplastic syndrome [n = 9]).

Conclusions: With longer follow-up, responses to liso-cel continue to be durable; the estimated OS rate at 5 y was 38.1% and estimated DSS rate at 5 y was 52.0%. Liso-cel showed similar median OS, 5-y OS rate, and 5-y DSS rate to those reported for ZUMA-1. Rates of grade ≥ 3 post-TE AEs were low, and no new safety signals were observed. These data support the curative potential of liso-cel in pts with R/R LBCL.

Disclosures: Abramson: Bristol Myers Squibb: Consultancy, Research Funding; Cellectis: Research Funding; Merck: Research Funding; Mustang Bio: Research Funding; Seagen Inc.: Research Funding; Interius BioTh: Consultancy; Incyte Corporation: Consultancy; Genmab US Inc: Consultancy; Genentech, a member of the Roche Group: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy; BeiGene Ltd: Consultancy; Caribou Biosciences Inc: Consultancy; Century Therapeutics: Consultancy; Epizyme Inc: Consultancy; AbbVie Inc: Consultancy; Foresight Diagnostics: Consultancy. Palomba: Synthekine: Consultancy; Novartis: Consultancy; Cellectar: Consultancy; Bristo Meyer Squibb: Consultancy. Gordon: Bristol Meyers Squibb, Kite Pharmaceuticals: Other: Advisory board; Janssen: Other: data and safety monitoring board ; Ono Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; nanoparticles for cancer therapy (HDL NP As Inducers of Ferroptosis in Cancer, PCT/US2020/051549; b) Nanostructures for Treating Cancer and Other Conditions, PCT/UlllllLS2013/027431): Patents & Royalties: nanoparticles for cancer therapy (HDL NP As Inducers of Ferroptosis in Cancer, PCT/US2020/051549; b) Nanostructures for Treating Cancer and Other Conditions, PCT/UlllllLS2013/027431). Lunning: Daiichi Sankyo, Fate Therapeutics, Genentech, Genmab, Ipsen, Janssen: Consultancy, Honoraria; Kite, Lilly, Incyte, Recordati, Regeneron, SeaGen, ViTToria: Consultancy, Honoraria; Abbvie, Acrotech, ADC Therapeutics, Astrazeneca, Britsol-Myers Squibb, Caribou, CRISPR,: Consultancy, Honoraria; AbbVie, Bristol Myers Squibb, Fate Therapeutics, Sana Therapeutics, Kite: Consultancy, Research Funding. Wang: Research to Practice: Honoraria; Scripps: Honoraria; Studio ER Congressi: Honoraria; South African Clinical Hematology Society: Honoraria; WedMD: Honoraria; ADC Therapeutics: Consultancy; Physicians Education Resources: Honoraria; Amphista Therapeutics Limited: Consultancy; Deciphera: Consultancy; bE Biopharma: Consultancy; Genentech: Consultancy, Research Funding; InnoCare: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Lilly: Consultancy, Research Funding; Miltenyi Biomedicine: Consultancy; Oncternal: Consultancy, Research Funding; Praxel: Consultancy; Pepromene Oncology: Consultancy; Juno Therapeutics: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Nurix: Honoraria; NIH: Honoraria; MSC National Research Institute of Oncology: Honoraria; Merck: Consultancy, Honoraria; MJH Life Sciences: Honoraria; Janssen: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Genmab: Honoraria, Research Funding; Dava Oncology: Honoraria; Catamount Medical Education: Honoraria; CAHON: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; BioInvent: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Arnason: BMS: Other: Speaker fees; Regeneron Pharmaceuticals, Inc.: Other: Speaker fees. Kamdar: Abbvie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Novartis: Research Funding; SeaGen: Speakers Bureau; TG Therapeutics: Research Funding. Maloney: Celgene: Research Funding; Novartis: Honoraria; Navan Technologies: Current equity holder in private company, Honoraria; Lyell Immunopharma: Honoraria; Interius: Honoraria; ImmPACT Bio: Honoraria; Gilead Sciences: Honoraria; Chimeric Therapeutics: Honoraria; Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy; Genentech: Consultancy, Honoraria; Caribou Biosciences: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Patents & Royalties: rights to royalties from Fred Hutch for patents licensed to Juno, Research Funding; Legend Biotech: Research Funding; A2 Biotherapeutics: Current holder of stock options in a privately-held company. Shadman: Koi Biotherapeutics: Current holder of stock options in a privately-held company; Mustang Bio, Genentech, AbbVie/Pharmacyclics, Beigene, AstraZeneca, Genmab, Morphosys/Incyte, Vincerx, BMS, TG Therapeutics: Research Funding; BMS: Other: Current employment of spouse; AbbVie/Pharmacyclics, Genentech, AstraZeneca, Genmab, Janssen, Beigene, Bristol Myers Squibb, Morphosys/Incyte, Kite Pharma, Eli Lilly, Fate Therapeutics, Nurix, Merck, ADC Therapeutics, MEI Pharma, MustangBio, Regeneron: Consultancy; Abbvie: Consultancy, Research Funding; Adaptimmune: Consultancy; Adaptive Biotechnologies: Consultancy; AstraZeneca: Consultancy, Research Funding; Atara Biotherapeutic: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Lilly: Consultancy; Epizyme: Consultancy; Fate Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; Innate Pharma: Consultancy; Kite, a Gilead Company: Consultancy; MEI Pharma: Consultancy; Merck: Consultancy; MorphoSys/Incyte: Consultancy, Research Funding; Mustang Bio: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Regeneron: Consultancy; Sound Biologics: Consultancy; TG Therapeutics: Consultancy, Research Funding; Celgene: Research Funding; Genmab: Research Funding; Gilead Sciences: Research Funding; Sunesis: Research Funding. Andreadis: Roche: Research Funding; Abbvie: Consultancy; Genmab: Research Funding; Seattle Genetics: Consultancy; Novartis: Research Funding; BMS: Consultancy; Merck: Research Funding; Astra Zeneca: Consultancy; Gilead/Kite: Consultancy. Sehgal: PeerView Live: Speakers Bureau; Bristol Myers Squibb: Research Funding; Gilead Sciences: Research Funding; Chimagen: Research Funding; Cytoagents: Research Funding. Ghosh: ADC Therapeutics: Consultancy; BeiGene: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Adaptive Biotech: Consultancy; Genmab: Consultancy; Gilead/Kite: Consultancy, Speakers Bureau; Incyte: Consultancy; Janssen: Consultancy, Speakers Bureau; Lava Therapeutics: Consultancy. Hidalgo-López: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Wang: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ogasawara: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Singh: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Siddiqi: BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Other: Ad board; Astra Zeneca: Speakers Bureau.

*signifies non-member of ASH