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) carries a poor prognosis. Responses to current therapies, including autologous stem cell transplantation (auto-HSCT) and chimeric antigen receptor T-cell (CAR-T) therapy, remains unsatisfactory, or with frequent early progression despite initial response. 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 with ASCT in combination (T-C group), while the remaining ten underwent CAR-T therapy alone (C group). We systematically compared 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) based on combined hematologic and imaging assessments of EMD. In contrast, among the 10 patients in the C group, 8 met hematologic criteria for ORR, but only 6 demonstrated 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 interleukin-6 (IL-6). On day 28 post-infusion, the proportion of CD3⁺CD4⁺ T cells were significantly greater in the T-C group. While cytokine release syndrome (CRS) tended to be more severe in this group, the incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS) were comparable between groups. Hematologic recovery was delayed in the T-C group, and three of eight patients developed poor graft function. Conclusion When followed up for more than 3 years, the combination of anti-BCMA CAR-T cell therapy and auto-HSCT was associated with improved PFS and OS in R/R MM patient with EMD. Moreover, CD4⁺ T cell dynamics might be associated with the durable clinical response observed in the T-C group. Although the T-C group experienced higher-grade CRS and more prolonged hematologic toxicity, no treatment-related deaths due to treatment-related toxicities were observed. (Trial registration: ChiCTR2000033925 )