Anti-CD19 chimeric antigen receptor (CAR) T cell therapies are efficacious and have been approved for the treatment of certain B cell leukaemias and lymphomas. CD19 is not typically expressed on the malignant plasma cells of multiple myeloma (MM), but a different B cell marker, B cell maturation antigen (BCMA), is expressed on these cells. Now, interim data from a phase I trial of a novel CAR T cell product validate BCMA as a therapeutic target in patients with MM.
The recently published data come from the first 33 patients treated with a single infusion of bb2121, comprising autologous T cells transduced with an anti-BCMA–4-1BB–CD3ζ CAR construct, as part of the CRB-401 trial. All patients were heavily pretreated (median of 7 prior lines of therapy, range 3–23). Across a dose range of 50–800 × 106 CAR T cells, the objective response rate (ORR) was 85% and the complete response (CR) rate was 45%, with evidence of a dose–response relationship. Most patients (n = 19) received 450 × 106 CAR T cells; in this group, the ORR was 95% and was similar in subgroups stratified by BCMA expression on <50% versus ≥50% of bone marrow plasma cells (100% and 91%, respectively). Of note, 16 patients with a response were evaluated for minimal residual disease (MRD) and all tested negative at a sensitivity of ≤10−4.
At a median follow-up duration of 11.3 months (minimum of 6.2 months), the median progression-free survival was 11.8 months; ~40% of responders had disease progression, with similar rates among those with a CR and/or a MRD-negative response. Thus, most responses are unlikely to persist.
Moreover, toxicities, although manageable, were common. Indeed, 97% of patients had at least one grade ≥3 adverse event (AE), predominantly haematological AEs (for example, neutropenia in 85%). Furthermore, the characteristic AEs of CAR T cell therapies were evident, with cytokine-release syndrome occurring in 76% of patients (grade 3 in 6%) and neurological AEs in 42% (one of grade 4).
These data are promising but emphasize the value of ongoing translational research to improve not only the efficacy but also the safety of CAR T cell therapies.
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Original article
Raje, N. et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl. J. Med. 380, 1726–1737 (2019)
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Killock, D. Anti-BCMA CAR T cells for MM. Nat Rev Clin Oncol 16, 465 (2019). https://doi.org/10.1038/s41571-019-0229-x
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DOI: https://doi.org/10.1038/s41571-019-0229-x
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