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)

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.

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:Bristol Myers Squibb: Consultancy, Research Funding; Abbvie: Consultancy; Genmab: Consultancy. 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.