Updated Results of the KarMMa Trial of Idecabtagene Vicleucel CAR T-Cell Therapy in Patients with RRMM

Updated results of the KarMMa trial showed that ide-cel CAR T-cell therapy resulted in durable and deep responses in heavily pretreated, triple-class–exposed patients with RRMM, supporting an overall favorable clinical benefit–risk profile.

Patients with relapsed/refractory multiple myeloma (RRMM) who were exposed to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies have poor outcomes with subsequent treatments. The pivotal KarMMa study (NCT03361748) demonstrated that the B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel) resulted in frequent, deep, and durable responses in triple-class–exposed patients with RRMM. Updated results of the KarMMa study were presented at the 2021 International Myeloma Workshop and summarized here.

The study enrolled patients who had received ≥3 previous regimens, had previous exposure to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies, and had disease refractory to their last regimen per International Myeloma Working Group criteria. Eligible patients received ide-cel infusion (target dose levels of 150-450 × 10⁶ CAR-positive T-cells) following 3 days of lymphodepletion (cyclophosphamide 300 mg/m² plus fludarabine 30 mg/m²). The primary end point was overall response rate (ORR); secondary end points included complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. The data cutoff date was December 21, 2020.

Of the 140 patients enrolled, 128 patients received ide-cel infusion. The median age of the study population (N = 128) was 61 years. Patients had received a median of 6 (range, 3-16) previous regimens, with 84% being triple-class refractory and 26% penta-refractory (lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab). Most patients (88%) had received bridging therapy.

In the total treated population, at a median follow-up of 24.8 months, 94 (73%) patients achieved an ORR, with a CR rate of 33%; median DOR was 10.9 months and PFS was 8.6 months. Among patients who achieved CR or better, median DOR was 21.5 months and median PFS was 22.4 months. There was a dose-response relationship, with improved outcomes achieved at higher doses. At 450 × 10⁶ CAR-positive T-cells, ORR was 81%, CR rate was 39%, median DOR was 11.3 months, and median PFS was 12.2 months; median DOR was not reached in patients who achieved a CR or better. All patient subgroups achieved ORRs, including those with high tumor burden (71%), extramedullary disease (70%), and Revised Multiple Myeloma International Staging System stage III disease (48%). Median OS was 24.8 months; the estimated 24-month OS rate was 51%.

The most common any grade adverse events were neutropenia and cytokine release syndrome (CRS). CRS occurred in 84% of patients and was mostly grade 1/2 severity. Five patients had grade 3 CRS and 1 patient had grade 4 CRS (at 300 × 10⁶); there was 1 death caused by CRS (at 300 × 10⁶). CRS was mostly managed with tocilizumab (N = 67) and steroids (N = 19). Neurotoxicity (investigator-assessed) was reported in 23 (18%) patients; 5 patients had grade 3 events, and none had grade ≥4 events. Neurotoxicity was managed with steroids (N = 10) and tocilizumab (N = 3).

Based on updated results of the KarMMa trial, it was concluded that ide-cel CAR T-cell therapy resulted in durable and deep responses in heavily pretreated, triple-class–exposed patients with RRMM, and a favorable clinical benefit–risk profile.

Source: Anderson LD Jr, Shah N, Jagannath S, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, for the treatment of patients with relapsed and refractory multiple myeloma (RRMM): updated results from KarMMa. Clin Lymphoma Myeloma Leuk. 2021;21(suppl 2):S17-S18.