Journal Article

BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma

Cheng, Qian, Chu, Ling, Kang, Liqing, Liu, Jing, Zhang, Jian, Wang, Erhua, Li, Xin, Liu, Rui, Deng, Zuqun, Tu, Yixuan, Wang, Liwen, Yu, Yan, Yan, Yuhan

2024

Overview

Background B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy. Methods We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro. Results The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1–14) months, while the OS (overall survival) was 10.7 (1.2–16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7–13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity. Conclusions Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Aged / B-Cell Maturation Antigen / BCMA CAR T-cell therapy / Biomedical and Life Sciences / Biomedicine / Care and treatment / Cell / Combination therapy / Combined Modality Therapy / Drug therapy, Combination / Female / Humans / Immunotherapy, Adoptive - adverse effects / Immunotherapy, Adoptive - methods / Male / Medical research / Medicine, Experimental / Medicine/Public Health / Middle Aged / Multiple myeloma / Multiple Myeloma - drug therapy / Multiple Myeloma - pathology / Multiple Myeloma - therapy / Neoplasm Recurrence, Local / Physiological aspects / Pomalidomide / Receptors, Chimeric Antigen / Recurrence / Relapsed/Refractory multiple myeloma (R/R MM) / Retrospective Studies / Thalidomide - analogs & derivatives / Thalidomide - therapeutic use / tissue and gene therapy / Treatment Outcome