POINT‐OF‐CARE ANTI‐BCMA CAR T‐CELL THERAPY INDUCES ENCOURAGING RESPONSE RATES IN HIGH‐RISK RELAPSED/REFRACTORY MULTIPLE MYELOMA

Abstract

Introduction: Anti-BCMA chimeric antigen receptor (CAR) T-cell therapy showed excellent efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). Point-of-care (POC) CAR manufacturing abrogates the need for cryopreservation and shipment of cells, thus shortening the manufacturing process and reducing the necessity of bridging therapy. We report outcomes of phase 1b/2 single-center clinical trial of autologous POC anti-BCMA CAR T-cell therapy in patients (pts) with R/R MM treated with ≥3 prior therapies (NCT05243212). Methods: Pts underwent a single peripheral blood leukapheresis. Fresh T-cells were transduced with retroviral vector encoding the anti-BCMA CAR (based on 11D5-3 ScFv, CD28 costimulatory domain, and CD3-ζ signaling domain). Cell dose was 6 × 106/kg (dose level I [n = 3]) or 9 × 106/kg (dose level II [n = 29]) CAR T-cells. Response was defined per IMWG criteria. Last follow-up was as of 02/2023. Results: All 32 pts (median age 60, IQR 54–67) enrolled received CAR T-cell infusion in a median of 11 days (IQR 11–11) after leukapheresis. Only 2 pts received bridging chemotherapy. The median number of prior therapies was 4 (IQR 3–5), with 59% and 34% of the pts being penta- and quad-refractory, respectively. 7 (22%) pts had prior exposure to BCMA-targeted therapy (belantamab mafodotin, n = 5 [16%]; talqeutamab, n = 2 [6%]). At enrollment, 10 (34%) pts had high-risk cytogenetics, 7 (22%) had double-hit myeloma, and 17 (57%) had extramedullary involvement. Only 17 (53%) and 2 (16%) pts were eligible to enroll in the KarMMa (NEJM, 2021) and CARTITUDE-1 (Lancet, 2021) studies, respectively. One patient (3%) developed grade 3 cytokine release syndrome. Immune effector cell-associated neurotoxicity syndrome was not noted. Grade 3–4 neutropenia and thrombocytopenia occurred in 31 (97%) and 16 (50%), respectively. Anemia requiring transfusion occurred in 14 (44%) pts. Cellular therapy-related death was not observed. The median follow-up was 3.9 months (IQR 2.6–7.3). Best Overall response rate (PR at least) was 59% (VGPR at least, 40%). Median time to first response was 31 days (95% CI: 26–33). Estimated 6-months OS, PFS and duration of response were 89% (95% CI: 75–100), 48% (95% CI: 33–72), and 63% (95% CI: 41–97), respectively. Patients with prior exposure to BCMA-targeted therapies had an inferior PFS (HR 3.4 [95% CI: 1.2–9.7] p = 0.03; Figure 1). Conclusion: POC anti-BCMA CAR T-cells induced high response rates with an excellent safety profile in high-risk MM patients mostly not eligible to be enrolled in the pivotal trials. The rapid CAR-T production time obviated the need for bridging therapy in most patients. It is noteworthy that prior exposure to BCMA-targeted therapies is associated with dismal PFS, hence those therapies should be carefully considered when CAR T-cell therapy might be intended. Encore Abstract—previously submitted to EHA 2023 Keywords: cellular therapies, multiple myeloma No conflicts of interests pertinent to the abstract. * H. Magen, E. Shkury and A. Avigdor contributed equally to the abstract.