P-041: Efficacy and safety of BCMA-specific CAR T cell-based therapy in relapsed/refractory multiple myeloma patients with extramedullary disease

Introduction: Relapsed/refractory (R/R) multiple myeloma (MM) patients with extramedullary disease (EMD) have an unfavorable prognosis and no effective treatment. B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown promising efficacy in R/R MM; however, data on patients with EMD remain limited. We aimed to assess the efficacy and safety of CAR T-cell therapy in R/R MM patients with EMD.

Methods: We conducted a retrospective multi-institutional study of 55 R/R MM patients confirmed with EMD at referral. The definition of EMD included (1) soft tissue masses in extraosseous locations resulting from hematogenous spread (EM-E) and (2) bone-related plasmacytomas that extend via disruption of cortical bones into contiguous soft tissues (EM-B). The overall response, long-term outcomes, and safety were assessed. We also characterized differential response between medullary and extramedullary disease, analyzed unique attributes of compartmental toxicity, and explored patterns of relapse in the setting of EMD.

Results: The infusion resulted in an overall response rate of 90.9% (95% confidence interval [CI], 80.4-96.1) in medullary disease and 70.9% (95% CI, 57.9-81.2) in EMD (P=0.008). Discrepant outcomes between medullary and extramedullary response were observed, with suboptimal and delayed overall response and shortened duration of response in the setting of EMD. With a median follow-up of 27.3 months, the median progression-free survival was 8.7 months (95% CI, 3.7-18.8), and the median overall survival was 16.0 months (95% CI, 13.5-20.1). Local cytokine release syndrome (CRS) was depicted in 21.8% patients and was associated with the occurrence of systemic CRS (r = 0.322; P = 0.017). 80% patients experienced post-infusion progression in EMD, and BCMA+ progression constituted the main pattern of progression in EMD. Landmark analysis was conducted to compare OS in patients who progressed versus remained progression-free at the 6-month landmark time point. We demonstrated that progression before 6 months post-infusion is strongly associated with an increased risk of death (HR = 11.15 [95% CI, 3.49 to 35.60]; P < 0.001).

Conclusions: Our study shows that anti-BCMA CAR-T therapy has provided apparent therapeutic advantage over the existing drugs in response rate and long-term survival. We describe a discrepancy between medullary and extramedullary response towards CAR T-cell therapy. We suggest that BCMA-specific CAR T cell-based therapy may have limited efficacy in EMD, perhaps due to insufficient expansion and persistence of CAR T cells within the microenvironment.