Phase 2 results of idecabtagene vicleucel (ide-cel, bb2121) in Japanese patients with relapsed and refractory multiple myeloma

Abstract

Background: In the phase 2 KarMMa trial, patients with relapsed/refractory multiple myeloma (RRMM) achieved deep and durable responses with idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy. Here we report a sub-analysis of the Japanese cohort of KarMMa.

Methods: Adult patients with RRMM who had received ≥ 3 prior treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, and had disease refractory to last treatment received ide-cel at a target dose of 450 × 10⁶ CAR positive T cells.

Results: Nine patients were treated with ide-cel. The overall response rate was 89% (median follow-up, 12.9 months). The best overall response was stringent complete response in 5 patients (56%), very good partial response in 3 (33%), and stable disease in 1. Median duration of response was not reached. All patients experienced grade ≤ 2 cytokine release syndrome and one patient experienced grade 2 neurotoxicity, but all resolved. Two patients died, one each from plasma cell myeloma and general health deterioration.

Conclusion: Ide-cel yielded deep, durable responses with a tolerable and predictable safety profile in Japanese patients with RRMM. These results are similar to those of the non-Japanese population in KarMMa.

Keywords: CAR T cell therapy; Idecabtagene-vicleucel; Japanese patients; Relapsed/refractory multiple myeloma; Triple-class exposed.

Fig. 1

Study design and patient disposition. CAR chimeric antigen receptor, CR complete response, Cy cyclophosphamide, DOR duration of response, Flu fludarabine, HEOR health economics and outcomes research, ide-cel idecabtagene vicleucel, IMWG International Myeloma Working Group, MRD minimal residual disease, ORR overall response rate, OS overall survival, PFS progression-free survival, PI proteasome inhibitor, PK pharmacokinetics, QOL quality of life, RRMM relapsed/refractory multiple myeloma, TTR time to response. a Defined as documented disease progression during or within 60 days from last dose of prior antimyeloma regimen. b Based on 1 manufacturing failure in the non-Japan cohort out of 149 patients in Japan and non-Japan cohorts who underwent leukapheresis (target dose levels 150–450 × 10⁶ CAR+ T cells). c Hospitalization for 14 days was required after infusion. d By next-generation sequencing

Fig. 2

Kinetics of response. The response assessments in the treated population were according to the IMWG criteria and adjudicated by the independent review committee. A square indicates when the response was recorded. CR/sCR complete response/stringent complete response, PD progressive disease, PR partial response, VGPR very good partial response

Fig. 3

Cellular kinetics. Data cutoff for transgene data was April 7, 2020. sBCMA soluble B-cell maturation antigen