Transcend fl: phase 2 study results of lisocabtagene maraleucel (liso‐cel) in patients (pts) with relapsed/refractory (r/r) follicular lymphoma (fl)

Introduction: Pts with R/R indolent NHL (iNHL), particularly those with high-risk features, have poor outcomes. TRANSCEND FL (NCT04245839), a global, phase 2, single-arm, multicohort, pivotal study assessed efficacy and safety of the anti-CD19 CAR T cell therapy liso-cel in pts with R/R iNHL. We report primary analysis results in pts with R/R FL, with safety in all liso-cel–treated pts (i.e., second-line or later [2L+] pts; safety set) and efficacy focused on pts in third line or later (3L+). Methods: Eligible pts with R/R FL included 3L+ pts and second-line (2L) pts with disease progression within 24 mo (POD24) of diagnosis and/or modified Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria. All pts received ≥1 prior combination systemic therapy, including an anti-CD20 antibody and an alkylator. Pts received liso-cel (100 × 106 CAR+ T cells) after lymphodepleting chemotherapy. Bridging therapy was allowed. 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 PK. Pharmacodynamics (PD) were exploratory. Results: At data cutoff (January 27, 2023), of 139 leukapheresed pts, 130 (94%) received liso-cel, 5 received nonconforming product, and 124 (89%) were efficacy evaluable (EE) per IRC. In pts with 3L+ FL, median (range) age was 62 y (23–80), 89% had Ann Arbor stage III/IV disease, and 57% were high-risk per FL International Prognostic Index. Forty-three percent of pts had POD24, 53% met GELF criteria, and 64% were double refractory to anti-CD20 antibody and an alkylator. Median (range) prior lines of therapy was 3 (2–10). Median (range) follow-up was 18.9 mo (0.3–28.2). In EE pts with 3L+ FL (n = 101), the primary endpoint of ORR was met at 97.0% (95% CI, 91.6–99.4; one-sided P < 0.0001; Table). CR rate was 94.1% (95% CI, 87.5–97.8; one-sided P < 0.0001). With a median follow-up of 16.6 mo and 17.5 mo, respectively, median DOR and PFS were not reached; 12-mo DOR and PFS were 81.9% and 80.7%, respectively. ORR, CR rate, DOR, and PFS were similar in EE pts with 2L+ FL. In the safety set (2L+ FL, n = 130), the most common grade (gr) ≥3 treatment-emergent adverse events (TEAE) were cytopenias; neutropenia was most frequent (65%). One TEAE death due to gr 5 macrophage activation syndrome occurred. Cytokine release syndrome (CRS) occurred in 58% of pts (gr 3, 1%; no gr 4–5) and neurological events (NE) in 15% (gr 3, 2%; no gr 4–5; Table). Prolonged cytopenia (gr ≥3 laboratory values at Day 29) occurred in 22% of pts and gr ≥3 infection in 5%. PK/PD data will be presented. Conclusions: In pts with R/R FL, liso-cel demonstrated clinically meaningful benefit, with high response rates that were durable, and a favorable safety profile, with low rates of gr ≥3 TEAEs of CRS/NEs, prolonged cytopenia, and infection. The research was funded by: This study was funded by Celgene, a Bristol-Myers Squibb Company. All authors contributed to and approved the abstract; writing and editorial assistance were provided by Amy Agbonbhase, PhD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb. Keyword: Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract F. Morschhauser Consultant or advisory role Gilead, Novartis, BMS, Roche, Genmab, Abbvie Honoraria: Roche, Chugai Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Gilead, Astra Zeneca, Abbvie S. Dahiya Other remuneration: Advisory board: BMS M. L. Palomba Consultant or advisory role Novartis, Cellectar, Synthekine, Kite, Seres, Magenta, WindMIL, Rheos, Nektar, Notch, Priothera ,Ceramedix, Lygenesis, Pluto Stock ownership: Juno, Seres Research funding: Seres Other remuneration: Royalties or licenses: Juno, Seres; Patents planned, issued or pending: Juno, Seres A. M. Garcia-Sancho Consultant or advisory role Roche, BMS/Celgene, Kyowa Kirin, Clinigen, Eusa Pharma, Novartis, Gilead/Kite, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Ideogen, Abbvie Honoraria: Roche, BMS/Celgene, Janssen, Gilead/Kite, Takeda, Eusa Pharma, Novartis Educational grants: Gilead/Kite, Janssen, Roche, BMS/Celgene Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: BMS J. L. Reguera Ortega Honoraria: Kite/Gilead, Novartis, Janssen, Sanofi, Amgen, BMS Educational grants: Kite/Gilead, Janssen J. Kuruvilla Consultant or advisory role Abbvie, Antengene, BMS, Gilead, Karyopharm, Merck, Roche, Seattle Genetics Honoraria: Abbvie, Amgen, Astra Zeneca, BMS, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics Research funding: Roche, Astra Zeneca, Merck Educational grants: Kite Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Karyopharm; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Lymphoma Canada U. Jager Honoraria: BMS, Novartis, Gilead, Miltenyi, Janssen and Roche Other remuneration: supported by the Innovative Medicines Initiative (IMI) T2EVOLVE and receives funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 945393. This Joint Undertaking receives support from the European Union ́;s Horizon 2020 research and innovation program and EFPIA. G. Cartron Consultant or advisory role BMS, Roche, Abbvie, MedXcell, Ownards Therapeutic, MabQi Honoraria: Gilead, Jansen, Novartis, Roche, BMS, Abbvie K. Izutsu Consultant or advisory role Otsuka, Kyowa Kirin, Genmab, Tanabe Mitsubishi Honoraria: Bristol Myers Squibb, AstraZeneca, Eisai Zenyaku, Kyowa Kirin, Takeda, Chugai, Novartis, MSD, SymBio, Nihon Shinyaku, Abbvie, Ono Pharmaceutical, Pfizer, Eli Lilly, Meiji Seika Pharma, Daiichi Sankyo Other remuneration: Grants or contracts from any entity: Chugai, Otsuka (paid to institution) M. Dreyling Honoraria: Astra Zeneca, Beigene, Gilead/Kite, Janssen, Lilly, Novartis, Roche Research funding: Abbvie, Bayer, BMS/Celgene, Gilead/Kite, Janssen, Roche Other remuneration: Advisory board: Abbvie, Astra Zeneca, Beigene, BMS/Celgene, Gilead/Kite, Janssen, Lilly/Loxo, Novartis, Roche B. Kahl Consultant or advisory role BMS and Kite Pharmaceuticals H. Ghesquieres Consultant or advisory role Gilead, Roche Honoraria: Gilead, Roche, BMS, Abbvie K. Ardeshna Educational grants: Novartis, Gilead, BMS H. Goto Honoraria: BMS, Novartis, Kite, Chugai, Daiichi-Sankyo, Kyowa-Kirin, Symbio, MSD Other remuneration: Grants or contracts from BMS, Symbio, Kyowa-Kirin. J. S. Abramson Consultant or advisory role Celgene, Novartis, Abbvie, Kite, Genetech, EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, BMS, BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MustangBio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda, C4 Therapeutics Honoraria: Regeneron, AstraZeneca, Janssen, BMS/Celgene Research funding: Seattle Genetics, AI Therapeutics, BMS/Celgene I. Fleury Consultant or advisory role Abbvie, AstraZeneca, Beigene, Celgene, Incyte, Janssen, Kite-Gilead, Merck, Novartis, Roche, Seagen Honoraria: Abbvie, Beigene, BMS, Incyte, Janssen, Kite-Gilead, Merck, Novartis, Roche, Seagen S. Mielke Honoraria: Celgene/BMS: Novartis: Janssen: Gilead/KITE: JSMO: Pfizer Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: Immunicum/Mendes, Miltenyi. Founder/Leadership (via my institution): SWECARNET. Founder (spouse): ScientifyResearch T. Farazi Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb Other remuneration: Patents: Bristol Myers Squibb O. Fasan Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb J. Lymp Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb M. Vedal Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb R. Nishii Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb A. Avilion Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb J. Papuga Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb L. J. Nastoupil Consultant or advisory role Sirpant, Incyte, Abbvie, Regeneron Honoraria: Gilead/Kite Educational grants: Genentech Other remuneration: Participation on a Data Safety Monitoring Board or Advisory Board: DeNovo, MEI, Genentech, Takeda BMS, Caribou Biosciences, Daiichi Sankyo, Gilead, Janssen, Merck, Novartis, Takeda