Key predictors of long-term outcomes in BCMA-targeted CAR-T therapy for relapsed/refractory multiple myeloma.

Background: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy exhibits high response rates in patients with relapsed/refractory multiple myeloma (r/r MM). However, the specific factors that influence the response duration remain poorly understood.

Methods: This single-centre, retrospective observational study included 56 patients with r/r MM who received BCMA CAR-T therapy (equecabtagene autoleucel) at Tongji Hospital, China. We analysed response rates and long-term clinical outcomes and identified key factors contributing to the long-term efficacy of BCMA CAR-T therapy.

Results: At a median follow-up of 39.6 months, the overall response rate (ORR) was 96.4%. Among the patients, 96.4% (54 of 56) achieved minimal residual disease (MRD) negativity, whereas 80.4% (45 of 56) achieved complete response (CR) or stringent complete response (sCR). Poorer outcomes were observed in patients with triple exposure, high cytogenetic risk, or failure to achieve CR. Better outcomes were associated with a CAR-T cell persistence of at least six months and sustained MRD negativity. Prolonged MRD negativity was strongly correlated with longer progression-free survival (PFS), with median PFS durations of 58 months, 64 months, and not reached (NR) for patients who maintained MRD negativity for 12, 24, and 36 months, respectively. Patients who remained MRD-negative and progression-free exhibited higher CAR-T cell expansion peaks. Additionally, CAR-T cell persistence was positively correlated with the duration of MRD negativity duration, PFS, and overall survival (OS).

Conclusions: BCMA CAR-T therapy provides durable responses in a subset of patients with r/r MM. Early intervention may improve patient prognosis by promoting sustained MRD negativity, thus improving overall treatment outcomes.

Trial Registration: Trial registration Chinese Clinical Trial Registry, ChiCTR2000033946 ( https://www.chictr.org.cn/showproj.html?proj=53503 ), Registered June 18, 2020. Trial registration Chinese Clinical Trial Registry, ChiCTR1800018137 ( https://www.chictr.org.cn/showproj.html?proj=30653 ), Registered August 31, 2018.