Chief of hematology department Shanghai SinoUnited Hospital, China Shanghai, Shanghai, China (People's Republic)
Introduction: Extramedullary disease (EMD) in relapsed/refractory multiple myeloma (RRMM) presents a significant clinical challenge due to its aggressive nature, rapid progression, and resistance to conventional treatments. Despite promising improvements observed with BCMA-CAR T therapy, outcomes for EMD-MM patients remain suboptimal, characterized by significantly lower overall response rates (ORRs) and shorter median progression-free survival (PFS).
Methods: To address this critical unmet need, this study retrospectively evaluated the clinical efficacy and safety of a novel tri-modal strategy, which integrates radiotherapy bridging, BCMA CAR-T cell therapy, and post-CAR-T maintenance, specifically designed to overcome EMD resistance. We retrospectively analyzed 10 consecutive R/R EMD-MM patients from three centers who received fully humanized BCMA-CAR T therapy (equecabtagene autoleucel) with bridging radiotherapy (10-30Gy) and maintenance therapy with IMiDs or Chidamide (CAR-T group). This cohort was compared to 10 retrospecitively propensity-matched patients who received standard of care (SOC) treatments during the same period (SOC group). All patients in both groups had progressed after more than two lines of previous treatments.
Results: CAR-T group demonstrated 100% ORR at six months, significantly higher than the 10.0%(1/10) ORR observed in the control group (p < 0.001). There was 100% CR rate at six months and Kaplan-Meier analysis revealed significantly superior PFS in the CAR-T cohort, with the median PFS not reached, compared to just 3.0 months in the SOC group (HR=0.03, 95% CI: 0.01–0.15, p< 0.001). All CAR-T recipients maintained continuous CR throughout the follow-up period (median 14.5 months, range 6–24 months), whereas 90% of SOC patients progressed within 12 months. The 12-month PFS rate was 100% for the CAR-T group versus 10% for the SOC group (p< 0.001 by log-rank test).Median OS was not reached in CAR-T group (0% mortality at median follow-up of 14 months) versus 5.5 months (IQR: 3.0–12 months; 90% mortality within 12 months).
Conclusions: This retrospective analysis of fully humanized BCMA-CAR T therapy in high-risk RRMM patients with EMD confirms profound efficacy, including extramedullary disease clearance and sustained remissions . Despite predictable and manageable toxicities (e.g., mild CRS, hematologic events), patients prognosis markedly improved. Future research will be needed to prioritize optimized bridging/maintenance strategies—including drug sequencing, dosing, and response-adapted regimens to maximize durable efficacy while minimizing risks through personalization.
