Objective To investigate the clinical characteristics and survival prognosis of patients with triple/quad-class exposed relapsed or refractory multiple myeloma (RRMM).

Methods  The clinical data of patients with triple/quad-class exposed RRMM from eight centers in Shanxi Province between May 2017 and May 2024 were retrospectively analyzed. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were examined by the Cox proportional hazards model and Log-rank test.

Results Among the 112 patients with triple-class exposure, 16 were quadruple-class exposed. The detection rates of high-risk cytogenetic abnormalities and extramedullary lesions in patients with triple-class exposure were 57.1% and 36.6%, respectively, while those in patients with quadruple-class exposure were 87.5% and 62.5%, respectively. The median PFS and OS of patients with triple-class exposure were 5.6 months and 12.2 months, respectively, while those of patients with quadruple-class exposure were 9.4 months and 16.9 months, respectively. Cox model analysis showed that extramedullary lesions and multi-line treatment (≥3 lines) were independent risk factors for the survival of patients with triple-class exposed RRMM (P<0.05). Previous autologous stem cell transplantation, subsequent conventional drug treatment, and B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) treatment were protective factors (P<0.05). After triple-class drug resistance, the Log-rank test verified that BCMA CAR-T treatment significantly prolonged the median PFS of patients compared to conventional drug treatment (9.4 months vs. 5.2 months, P=0.026 9), whereas the difference in OS was not statistically significant (16.9 months vs. 7.9 months, P=0.263 4).

Conclusions Patients with triple/quad-class exposed RRMM have a poor prognosis, and BCMA CAR-T cell therapy can improve survival in patients with triple-class drug-resistant RRMM.