Anti-BCMA CAR-T cell therapy for refractory / relapsed multiple myeloma: clinical experience of a center

Objective. To evaluate the clinical efficacy of anti-BCMA CAR-T cells in patients with refractory / recurrent multiple myeloma (RRMM.)

Materials and methods. Six patients with multiple myeloma MM who had undergone significant pretreatment got anti-BCMA (B-Cell Maturation Antigen) CAR-T (Chimeric Antigen Receptor) cell therapy at the clinical site of the Republican Research Center for Radiation Medicine and Human Ecology. Prior to CAR-T cell therapy, all patients got three to five lines of treatment, including autologous hematopoietic stem cell transplantation (auto-HSCT). The follow-up period ranged from 3 to 13 months (median is 9.5 months). The creation of a chimeric antigen receptor (CAR) for the MM target — BCMA protein, the generation of a model cell line with ectopic BCMA expression, and leukapheresis were performed at the Genetic Biotechnology Laboratory of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. The lymphodepletion regimen included cyclophosphamide and fludarabine. BCMA CAR-T cell levels were monitored by flow cytometry in peripheral blood on days 3, 7, 14, 28, and 60. The response to therapy, the dynamics of minimal residual disease, the persistence of BCMA CAR-T cells, and disease recurrence were analyzed.

Results. Persistence of CAR-T cells in the peripheral blood of patients from 7 to 14 days after administration of the cell product was detected in 5 of 6 patients. The time of peak CAR-T expansion correlated with the maximum antitumor response, expressed as the absence of clinical and laboratory signs of tumor growth. The most common adverse event associated with immune effector cells was hematological toxicity which developed in all patients.

Conclusion. CAR-T cell therapy targeting BCMA demonstrated high efficacy in the treatment of patients with refractory / recurrent MM with an acceptable safety profile. Overall response rates to anti-BCMA CAR-T cell therapy resulted in complete remission by day 28 and were 100%. Relapses occurred in two patients during the follow-up period. The absence of relapse has been recorded in 66.7% of cases to date, which can be regarded as a promising start.

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