Prior ASCT Has a Negative Impact on Outcomes in Relapsed/Refractory Multiple Myeloma Patients after BCMA CAR-T Therapy

Background

Despite the promising efficacy of BCMA CAR-T cell therapy in relapsed or refractory multiple myeloma (R/RMM), some patients relapse after initially responding to the treatment. Analyzing risk factors and proposing refined CAR-T cell therapy strategies is crucial to improving the prognosis of these patients.

Methods

From July 30, 2018, to September 27, 2023, 141 R/RMM patients who were receiving BCMA CAR-T therapy were enrolled. Logistic regression, Cox regression and competing risk analyses were employed to identify risk factors associated with the prognosis. Flow cytometry was conducted to measure the proportion of CAR-T cells within the total T cell population, monitoring the post-infusion dynamics of CAR-T cells.

Results

During the median follow-up of 20.2 months, the objective response rate (ORR) was 94.8%, with 50.7% of patients achieving a complete response (CR). The median progression free survival (PFS) was 15.2 months (95% CI: 7.6-22.8). Prior autologous stem cell transplantation (ASCT) was associated with lower CR rate (RR, 0.352 [95% CI: 0.149-0.830]; P = 0.017). Among 68 CR cases, patients with extramedullary disease (HR, 2.381 [95% CI: 1.108-5.116]; P = 0.026), and prior treatment with ASCT (HR, 3.622 [95% CI: 1.420-9.237]; P = 0.007) had higher cumulative incidences of relapse (CIR). Extramedullary disease (HR, 2.095 [95% CI: 1.310-3.349]; P = 0.002) and prior ASCT (HR, 2.272 [95% CI: 1.314-3.929]; P = 0.003) were identified as risk factors for poor PFS. Extramedullary disease (HR, 2.033 [95% CI: 1.104-3.744]; P = 0.023) was significantly associated with shortened overall survival (OS).

Further investigation into potential mechanisms revealed that, among the 136 patients with expansion peak data, the peak of CAR-T cell expansion was significantly lower in the ASCT group compared to the non-ASCT group (74.8% vs. 89.8% , P < 0.001).

Conclusions

Our study found that prior ASCT and extramedullary disease serve as adverse prognostic factors in R/RMM patients undergoing BCMA CAR-T cell therapy. Research on the adverse effects of prior ASCT revealed it impaired the peak expansion of CAR-T cells in vivo. Moving forward, we will conduct an in-depth study on the mechanisms by which extramedullary disease affects CAR-T cell therapy outcomes in the near future.

No relevant conflicts of interest to declare.