Deep and durable responses with ide-cel in RRMM

Updated results from the CRB-401 study demonstrated deep and durable responses with idecabtagene vicleucel (ide-cel), in heavily pretreated patients with relapsed and/or refractory multiple myeloma (R/R MM). In this highly triple-class-exposed population, median overall survival (OS) was 34.2 months and half of ongoing responders achieved duration of response (DOR) >2 years [1].

Patients with R/R MM previously exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies have poor outcomes with subsequent regimes. Deep and durable responses are uncommon, median progression-free survival (PFS) is 2-6 months, and median OS is <12 months. Ide-cel, a B-cell maturation antigen (BCMA)-directed chimaeric antigen receptor (CAR) T-cell therapy, demonstrated tolerability and promising efficacy in patients with R/R MM in the first-in-human phase 1 CRB-401 study (NCT02658929) and in the pivotal phase 2 KarMMa study (NCT03361748) [2,3]. Dr Yi Lin (Mayo Clinic, Minnesota, USA) reported updated safety and efficacy results for 62 patients who received ide-cel in the ongoing CRB-401 study. The expansion phase enrolled patients who had received ≥3 prior lines of therapy and were refractory to their last line of therapy [1].

The overall response rate (ORR) was 76%, including 24 patients (39%) with a complete response (CR) or better and 40 patients (65%) with a very good partial response or better. The median DOR was 10.3 months. The most frequent adverse events (AEs) were neutropenia (92%), cytokine-release syndrome (76%), anaemia (76%), and thrombocytopenia (74%). The most frequent grade 3/4 AEs were neutropenia (89%), leukopenia (61%), anaemia (57%), and thrombocytopenia (57%).

Efficacy and safety reflect prior reports and support a favourable clinical risk-benefit profile for ide-cel at a target dose level of ≥150 x 10⁶ CAR-positive T cells. These results are in concordance with results from the phase 2 KarMMa trial, showing that ide-cel treatment resulted in favourable risk-benefit profile in this patient population. In the latter trial, ORR was 73%, including CR rate of 33%, median DOR 10.7 months, median PFS 8.8 months, and median OS 19.4 months [3].

Ide-cel is currently being explored in multiple ongoing clinical trials: KarMMa-2 (NCT03601078), KarMMa-3 (NCT03651128), and KarMMa-4 (NCT04196491).

1. Lin Y, et al. Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma: Updated Results from Phase 1 CRB-401 Study. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 131.
2. Raje N, et al. N Engl J Med. 2019;380:1726-37.
3. Munshi NC, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results. 2020 ASCO Annual Meeting, 29-31 May. Abstract 8503.

Posted on 18 February 20214 September 2023