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Clinical Trial
. 2023 May;117(5):729-737.
doi: 10.1007/s12185-023-03538-6. Epub 2023 Jan 24.

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

Daisuke Minakata  1 , Tadao Ishida  2 , Kiyoshi Ando  3 , Rikio Suzuki  3 , Junji Tanaka  4   5 , Shotaro Hagiwara  4   5 , Revathi Ananthakrishnan  6 , Shigeki Kuwayama  7 , Mitsufumi Nishio  7 , Yoshinobu Kanda  8 , Kenshi Suzuki  2
Affiliations
Clinical Trial

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

Daisuke Minakata et al. Int J Hematol. 2023 May.

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.

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Conflict of interest statement

DM: nothing to declare. TI: grants or contracts from Alexion, Bristol Myers Squibb, Janssen, Pfizer, and Takeda; payment or honoraria from Bristol Myers Squibb, Janssen, ONO, Sanofi, and Takeda. KA: research funding from Chugai, Kyowa Kirin, and Takeda. RS: payment or honoraria from Janssen. JT: nothing to declare. SH: research funding from and participation on advisory board for Bristol Myers Squibb. RA: employee and stockholder of Bristol Myers Squibb; leadership or fiduciary role in other board, society, committee, or advocacy group for ASA NJ Princeton-Trenton Chapter (President). SK and MN: employee and stockholder of Bristol Myers Squibb K.K. YK: research grants from Bristol Myers Squibb, ONO, and Takeda; payment or honoraria for lectures from Bristol Myers Squibb, Janssen, Novartis, Sanofi, and Takeda. KS: honoraria from AbbVie, Amgen, Bristol Myers Squibb, Janssen, Novartis, ONO, Sanofi, and Takeda; consulted for Amgen, Bristol Myers Squibb, and Takeda; received research funding from Bristol Myers Squibb.

Figures

Fig. 1
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
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
Fig. 3
Cellular kinetics. Data cutoff for transgene data was April 7, 2020. sBCMA soluble B-cell maturation antigen
See this image and copyright information in PMC

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