EFFICACY AND SAFETY OF TISAGENLECLEUCEL (TISA‐CEL) IN ADULT PATIENTS (PTS) WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (R/R FL): PRIMARY ANALYSIS OF THE PHASE 2 ELARA TRIAL (2021)

Introduction: Most pts with r/r FL experience multiple relapses and progressively worse clinical outcomes with each line of therapy, underlining a need for novel therapies. Tisa-cel has demonstrated durable responses and manageable safety in adult pts with r/r diffuse large B-cell lymphoma. Here we report the primary analysis of ELARA (NCT03568461), an international, single-arm phase 2 trial of tisa-cel in adult pts with r/r FL. Methods: Eligible pts (≥18 y) had r/r FL (grades [Gr] 1-3A) after ≥2 lines of therapy or had failed autologous stem cell transplant. Bridging therapy was permitted followed by disease assessment prior to tisa-cel infusion. Pts received tisa-cel (0.6-6×108 CAR+ viable T cells) after lymphodepleting chemotherapy. The primary endpoint was complete response rate (CRR) by central review per Lugano 2014 criteria. Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and cellular kinetics. Predefined primary analysis occurred when ≥90 treated pts had ≥6 mo of follow-up. Results: As of September 28, 2020, 98 pts were enrolled and 97 received tisa-cel (median follow-up, 10.6 mo). At study entry, median age among treated pts was 57 y (range, 29-73), 85% had stage III-IV disease, 60% had a FLIPI score ≥3, 65% had bulky disease, and 42% had LDH > upper limit of normal. The median number of prior therapies was 4 (range, 2-13); 78% of pts were refractory to their last treatment (76% to any ≥2 prior regimens) and 60% progressed within 2 y of initial anti-CD20–containing treatment. Of 94 pts evaluable for efficacy, the CRR was 66% (95% CI, 56-75) and the ORR was 86% (95% CI, 78-92). CRRs/ORRs were comparable among key high-risk subgroups. Estimated DOR (CR) and PFS rates at 6 mo were 94% (95% CI, 82-98) and 76% (95% CI, 65-84), respectively. Of 97 pts evaluable for safety, 65% experienced Gr ≥3 adverse events within 8 weeks post-infusion, most commonly neutropenia (28%) and anemia (13%). Any-grade cytokine release syndrome (per Lee scale) occurred in 49% of pts (Gr ≥3, 0%). Any-grade neurological events (per CTCAE v4.03) occurred in 9% of pts (Gr 3, 0%; Gr 4, 1 pt and recovered). Three pts died from progressive disease. Cellular kinetic parameters for tisa-cel were estimated using transgene levels (by qPCR) in peripheral blood. Cmax and AUC0-28d were similar between responders (CR or partial response) and non-responders (stable or progressive disease). Maximum transgene levels were reached by a median of 10 days in responders and 12.9 days in non-responders; transgene persistence was detected up to 370 days and 187 days, respectively. Conclusions: These data demonstrate the efficacy and acceptable safety of tisa-cel in pts with r/r FL, including high-risk pts after multiple lines of prior therapy, and suggest that tisa-cel may be a promising therapy for pts with r/r FL. EA – previously submitted to ASCO 2021. The research was funded by: Novartis Keywords: Indolent non-Hodgkin lymphoma, Cellular therapies Conflicts of interests pertinent to the abstract S. J. Schuster Consultant or advisory role: Celgene, Nordic Nanovector, Novartis, Abbvie, Acerta Pharma/AstraZeneca, Alimera Sciences, BieGene, Juno Therapeutics, Luxo Oncology, Tessa Therapeutics, Genentech/Roche Honoraria: Novartis, Celgene Research funding: Novartis, Pharmacyclics, Adaptive Biotechnologies, Merck, Genentech/Roche, Celgene, Juno Therapeutics, Abbvie, Incyte, TG Therapeutics, DTRM M. Dickinson Consultant or advisory role: Novartis, BMS, Gilead Sciences, Roche, Janssen Honoraria: Roche, Amgen, MSD, Janssen, BMS, Novartis Research funding: Roche, Novartis, Takeda, Celgene, MSD Educational grants: Roche M. Dreyling Consultant or advisory role: Acerta Pharma/AstraZeneca, Bayer/Vital, Celgene/Jazz, Gilead Sciences, Janssen-Cilag, Novartis, Roche, BeiGene Honoraria: Bayer Health, Celgene, Gilead Sciences, Janssen-Cilag, Roche Pharma AG Research funding: Celgene, Janssen-Cilag, Roche Pharma AG, Abbvie Educational grants: Celgene, Janssen-Cilag, Roche Pharma AG J. Martinez-Lopez Consultant or advisory role: Janssen, Novartis, BMS, Incite, Astellas, Glaxo Stock ownership: Altum Sequencing Honoraria: Janssen, Novartis, BMS, Incite, Astellas, Glaxo Research funding: BMS, Roche A. Kolstad Consultant or advisory role: Nordic Nanovector Research funding: Merck, Nordic Nanovector Educational grants: Nordic Nanovector J. Butler Consultant or advisory role: Novartis Honoraria: Novartis M. Ghosh Research funding: Novartis, BMS L. Popplewell Honoraria: Roche, Pfizer Educational grants: Novartis J. C. Chavez Consultant or advisory role: Kite/Gilead, Novartis, Bayer, Karyopharm Therapeutics, Verastem, Pfizer, MorphoSys, TeneoBio, Celgene, Juno Therapeutics Honoraria: Kite/Gilead, Genentech, AstraZeneca, BeiGene Research funding: Merck E. Bachy Consultant or advisory role: Roche, Incyte Research funding: Takeda, Amgen Other remuneration: Non-financial support: Roche, BeiGene, Celgene, Incyte; Personal Fees: Roche, Janssen, Celgene, Novartis, Gilead K. Kato Consultant or advisory role: Abbvie, AstraZeneca, Celgene, Chugai, Janssen, Eisai, Novartis, Daiichi Sankyo Honoraria: Takeda, MSD, Kyowa-Kirin, Janssen, Celgene, Ono, Mundi, Dainippon-Sumitomo, BMS Research funding: Chugai, Takeda, Kyowa-Kirin, Abbvie, Eisai, Novartis, Celgnene, Ono, Daiichi Sankyo H. Harigae Honoraria: BMS, Novartis, Chugai, Jansseb Research funding: Astellas M. José Kersten Consultant or advisory role: Novartis, Kite/Gilead, Miltenyi Biotec, Takeda Honoraria: Novartis, Kite/Gilead, Roche Educational grants: Novartis, Kite/Gilead, Roche, Celgene C. Andreadis Employment or leadership position: Genentech/Roche (Recipient is an immediate family member) Consultant or advisory role: Kite/Gilead, Karyopharm Therapeutics, Atara Biotherapeutics, Incyte, TG Therapeutics, Epizyme Stock ownership: Genentech/Roche (Recipient is an immediate family member) Research funding: Novartis, GSK, Amgen, Juno Therapeutics, Celgene, Merck Educational grants: Kite/Gilead P. A. Riedell Consultant or advisory role: Kite/Gilead, Celgene/BMS, MorphoSys Takeda, Verastem, Karyopharm Therapeutics, Calibr, Bayer Educational grants: Novartis A. Zia Employment or leadership position: Novartis M. C. Morisse Employment or leadership position: Novartis N. H. Fowler Consultant or advisory role: Genentech/Roche, TG Therapeutics, Verastem, Bayer, Celgene, Novartis Research funding: Roche, Celgene, Novartis, Gilead Sciences, TG Therapeutics, Novartis, Abbvie, BeiGene C. Thieblemont Honoraria: Roche, Incyte, Novartis, Janssen, Bayer, Abbvie, Gilead sciences, Celgene Research funding: Roche Educational grants: Roche, Novartis, Kite/Gilead, Janssen-Cilag