Xu Jinhuan, Ming Xi, Wang Chunyan, Xu Bi, Xiao Yi
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R.China.
Medicine (Baltimore). 2021 May 7;100(18):e25784. doi: 10.1097/MD.0000000000025784.
Chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) have been used in the treatment of relapsed and refractory multiple myeloma (RRMM). The response rate and the depth of responses induced by anti-BCMA CAR-T cells are impressive. However, despite this, remissions are not sustained, and the majority of patients eventually relapse.
Two patients with multiple myeloma (MM) were selected to enroll in a phase I study involving anti-BCMA CAR-T cells (ChiCTR-OPC-16009113) because they did not have the good effect after traditional treatment. One is a 48-year-old male patient who received a diagnosis of IgG lambda MM in June 2015, he has received 4 cycles of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and obtained a complete response (CR). Approximately 11 months later, the disease progressed. Subsequent treatment included regimens incorporating liposomal doxorubicin, bortezomib, and dexamethasone (3 cycles); the response was poor, and the disease kept progressing. Another 65-year-old female patient received a diagnosis of IgG lambda MM in September 2016, she has received induction therapy with 1 cycle of bortezomib and dexamethasone (VD) and 4 cycles of lenalidomide and dexamethasone, the response was poor.
Both patients were diagnosed with RRMM according to the International Myeloma Working Group criteria.
Both patients received infusions of anti-BCMA CAR-T cells following an induction chemotherapy regimen of cyclophosphamide and fludarabine.
Both of them achieved a stringent CR at the 30th day with minimal residual disease-negative bone marrow by flow cytometry and serum monoclonal protein was undetectable at 4 and 10 months after cell transfusion. The CR has persisted in the 2 patients for >36 months.
Our findings demonstrate the anti-BCMA CAR-T cell treatment is a feasible therapeutic option for patients with RRMM. Fewer early lines of treatment may be beneficial to maintain the efficacy of CAR-T cells.
ChiCTR-OPC-16009113.
靶向B细胞成熟抗原(BCMA)的嵌合抗原受体T(CAR-T)细胞已被用于治疗复发难治性多发性骨髓瘤(RRMM)。抗BCMA CAR-T细胞诱导的缓解率和缓解深度令人印象深刻。然而,尽管如此,缓解并不持久,大多数患者最终复发。
两名多发性骨髓瘤(MM)患者因传统治疗效果不佳而入选一项涉及抗BCMA CAR-T细胞的I期研究(ChiCTR-OPC-16009113)。一名是48岁男性患者,2015年6月被诊断为IgG λ MM,他接受了4个周期的环磷酰胺、硼替佐米和地塞米松(CyBorD)治疗并获得完全缓解(CR)。大约11个月后,疾病进展。后续治疗包括含脂质体阿霉素、硼替佐米和地塞米松的方案(3个周期);反应不佳,疾病持续进展。另一名65岁女性患者2016年9月被诊断为IgG λ MM,她接受了1个周期硼替佐米和地塞米松(VD)的诱导治疗以及4个周期来那度胺和地塞米松治疗,反应不佳。
根据国际骨髓瘤工作组标准,两名患者均被诊断为RRMM。
两名患者在接受环磷酰胺和氟达拉滨诱导化疗方案后接受了抗BCMA CAR-T细胞输注。
两人均在第30天达到严格CR,流式细胞术检测骨髓微小残留病呈阴性,细胞输注后4个月和10个月血清M蛋白检测不到。CR在这两名患者中持续超过36个月。
我们的研究结果表明,抗BCMA CAR-T细胞治疗是RRMM患者可行的治疗选择。早期治疗线数较少可能有利于维持CAR-T细胞的疗效。
ChiCTR-OPC-16009113。