Long-term follow-up results of anti-BCMA CAR-T cell therapy combined with autologous hematopoietic stem cell transplantation in relapsed/refractory multiple myeloma with extramedullary disease.

BACKGROUND: Relapsed/refractory multiple myeloma (R/R MM) with extramedullary disease (EMD) has a poor prognosis. Responses to current therapies, including autologous hematopoietic stem cell transplantation (auto-HSCT) and chimeric antigen receptor (CAR) T-cell therapy, remain unsatisfactory or show frequent early progression despite an initial response. In this study, we aimed to investigate the efficacy of a therapeutic approach combining CAR T-therapy with auto-HSCT.

METHODS: Eighteen patients with R/R MM with EMD were enrolled in clinical trials evaluating anti-BCMA CAR-T therapy. Of these, eight patients were treated in combination with auto-ASCT in combination (T-C group), while the remaining ten underwent CAR T-cell therapy alone (C group). We retrospectively compared the clinical responses, CAR T-cell expansion kinetics, T-cell subset profiles, serum interleukin-6 (IL-6) levels, treatment-related toxicities, and long-term outcomes between the two cohorts.

RESULTS: In the T-C group, all 8 patients achieved an overall response (ORR) (ORR) based on the combined haematologic and imaging assessments of EMD. In contrast, among the 10 patients in the C group, 8 met the haematologic criteria for ORR, but only 6 demonstrated a radiographic response in EMD lesions. Progression-free survival (PFS) and overall survival (OS) were markedly improved in the T-C group. This cohort also exhibited higher peak levels of both CAR- T cells and IL-6. On day 28 post-infusion, the proportion of CD3⁺CD4⁺ T cells was significantly higher in the T-C group. While cytokine release syndrome (CRS) tended to be more severe in this group, the incidence and severity of the immune effector cell-associated neurotoxicity syndrome (ICANS) was comparable between the two groups. Haematologic recovery was delayed in the T-C group, and three of the eight patients developed poor graft function.

CONCLUSION: We retrospectively summarised the results of a 3-year follow-up and found that the combination of anti-BCMA CAR-T cell therapy and auto-HSCT was associated with improved PFS and OS in R/R MM patients with EMD. Moreover, CD4⁺ T-cell dynamics may be associated with the durable clinical response observed in the T-C group. Although the T-C group experienced higher-grade CRS and prolonged haematological toxicity, no treatment-related deaths due to treatment-related toxicities were observed. (Trial registration: ChiCTR2000033925).

TRIAL REGISTRATION: Registration center: Tianjin First Central Hospital.

TRIAL REGISTRATION NUMBER: ChiCTR2000033925. Registration Date: June 17, 2020. The patient gave their written informed consent in accordance with the Declaration of Helsinki. The patients agreed to have their data used in our study.