IMPACT OF RESPONSE TO SYSTEMIC BRIDGING THERAPY ON CLINICAL OUTCOMES AND CYTOKINE PROFILE IN PATIENTS RECEIVING CAR T‐CELL THERAPY FOR AGGRESSIVE B‐CELL LYMPHOMA

Abstract

Background: It is unclear whether a deeper response to bridging therapy (BT) before chimeric antigen receptor (CAR) T cell therapy improves CAR-T treatment outcome in large B cell lymphoma (LBCL). We studied the impact of response to systemic BT on clinical outcomes and cytokine profiles of LBCL patients (pts) treated with CD19-directed CAR-T. Methods: We included LBCL pts treated with systemic BT before receiving commercial CD19-CAR-T at two academic centers, and excluded those who received monotherapy with glucocorticosteroids or isolated radiation therapy. BT was classified as Polatuzumab- (pola) based, intensive chemotherapy, lenalidomide/ Bruton tyrosine kinases inhibitors (len/BTKi), or other. PET/CT scans obtained before and after BT, and after CAR-T were evaluated using Lugano 2014 response criteria. Association between BT and response rates (RR) were examined using Fisher’s exact test, and the associations with cytokine levels were examined using Kruskal Wallis tests. Kaplan Meier analysis was used to estimate overall (OS) and progression free survival (PFS) from time of CAR T infusion. Cox proportional hazards models were used for univariable and multivariable analyses. Results: We identified 148 pts whose median age was 65 (range 23–85), and 96 (65%) were male. BTs included: 62 (42%) pola-based, 48 (32%) intensive chemotherapy, 25 (17%) len/BTKi, and 13 (9%) other BT. Among all pts, 77 (52%) received Axicel, 42 (28%) received Tisacel and 29 (20%) received Lisocel. Median time from apheresis to CAR-T was 35 days. Among evaluable pts RR to BT were: 10 (7%) complete responses (CR), 39 (29%) partial responses (PR), 87 (64%) either stable disease (SD) or progressive disease (PD). RR did not differ among different BT regimens (p = 0.27). At day 100 post-CAR-T, RR were: 74 (50%) CR, 27 PR (18%) and 44 (30%) SD/PD. With a median follow up of 18.9 months, PFS was 5.03 months (95% CI: 3.25, 9.53) and median (OS) was 16.1 months (95% CI 12.2–31.3) (Figure 1A). In multivariable analysis, poor response to BT (SD/PD) and elevated LDH prior to CAR-T infusion were associated with worse PFS, but not with OS. LDH (Figure 1B), ferritin, IL-6, IL-10 and C-reactive protein measured prior to lymphodepletion (LD) and at day 0 of CAR-T infusion were significantly higher in pts with SD/PD compared to pts achieving a CR/PR to BT. Ferritin levels prior to LD were higher in pts who received intensive chemotherapy compared to other BT. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies Conflicts of interests pertinent to the abstract G. L. Shah Research funding: Janssen, Amgen, Beyond Spring, and BMS. DSMB for ArcellX M. Scordo Consultant or advisory role: McKinsey & Company, Angiocrine Bioscience, Inc., and Omeros Corporation; served on ad hoc advisory boards for Kite—A Gilead Company Honoraria: Received honoraria from i3Health and Medscape for CME-related activity Research funding: received research funding from Angiocrine Bioscience, Inc., and Omeros Corporation R. J. Lin Consultant or advisory role: Kite G. Salles Consultant or advisory role: Abbvie, Atbtherapeutics, Bayer, Beigene, BMS/Celgene, Debiopharm, Epizyme, Genentech/Roche, Genmab, Incyte, Ipsen, Janssen, Kite/Gilead, Loxo/Lilly, Molecular Partners, Morphosys, Nordic Nanovector, Novartis, Regeneron, Takeda H Stock ownership: Owkin M. Perales Consultant or advisory role: Adicet, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma. He serves on DSMBs for Cidara Therapeutics, Medigene, and Sellas Life Sciences, and the scientific advisory board of NexImmune. Research funding: He has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. Other remuneration: He has ownership interests in NexImmune, Omeros and OrcaBio. M. L. Palomba Consultant or advisory role: Synthekine, Cellectar, Beigene, Kite, BMS