P-228: Use of cilta-cel CAR T cells following previous use of a BCMA-directed CAR T-cell product in heavily treated patients with relapsed/refractory multiple myeloma: A single institution case series

Introduction: BCMA-directed CAR T-cell (CAR T) therapy has demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma (rrMM). Pivotal trials such as the KarMMa and CARTITUDE studies using ide-cel and cilta-cel, respectively, have shown ORR of 73% and 98%, leading to FDA approval of these products. Notably, ide-cel conferred a median OS of 19.4 months with a median DOR of 10.7 months. Similarly, cilta-cel conferred 27-month PFS and OS rates of 55% and 70.4%, respectively. Although these and real-world outcomes are promising, relapse after BCMA CAR T therapy remains a challenge.

Methods: This is a case series of 5 patients with rrMM from a single institution treated with BCMA-directed CAR T therapy between 2019-2022, followed by a second BCMA-directed CAR T therapy using cilta-cel at the time of relapse. Here we report the response and toxicity profile following the second CAR T therapy.

Results: Patients had a median age of 64 (40-76). 2 out of 5 patients had high risk disease based on cytogenetics. Prior to the second CAR T therapy, patients had received a median of 7 (5-8) lines of treatment including the first CAR T therapy. For the first CAR T therapy, 3 patients received an investigational BCMA-directed CAR T therapy at the recommended doses of the product and 2 patients received ide-cel. At the time of subsequent relapse all patients eventually received a second CAR T therapy with cilta-cel. ORR to first CAR T-cell therapy was 80%; 4 patients achieved ≥ VGPR (n=2 VGPR; n= 2 sCR), and 1 patient had PD, with a median DOR of 16 months (7-22 months) for responders. The time between two CAR T therapies ranged from 8-38 months, with all patients receiving at least 1 and up to 2 lines of treatment including bridging therapy before cilta-cel. At the time of this report, with a follow up ranging from 3.1-11 months after the second CAR T therapy, 4 out of 5 patients had achieved a response (n=3 CR; n=1 PR). One patient had refractory disease and required subsequent treatment. Notably, this was the same patient who had progressed on the previous CAR T cell therapy. Grade 2 CRS after cilta-cel was seen in 1 out of 5 patients. Hematologic toxicities were seen in all patients with grade 3-4 neutropenia in 5, grade 3 anemia in 3 and grade 4 thrombocytopenia in 2 patients. Prolonged grade 3-4 thrombocytopenia was seen in 1 responder requiring transfusions and thrombopoietin analogs. Three out of 4 responders had hypogammaglobulinemia with levels recovering in 2 patients within 8-12 weeks. One patient had prolonged hypogammaglobulinemia requiring IVIG beyond this time point.

Conclusions: This case series demonstrates the early efficacy and safety of a second BCMA-directed CAR T therapy, specifically in patients previously responsive to similar BCMA-directed therapy. This highlights the need to better understand the clinical utility of this approach and to delineate the heterogenous disease course and mechanism of resistance post BCMA CAR T therapy.