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抗BCMA嵌合抗原受体T细胞治疗复发难治性多发性骨髓瘤患者后的长期无事件生存期:两例病例报告

Long event-free survival after anti-BCMA CAR-T cell treatment for relapsed and refractory multiple myeloma patients: Two case reports.

作者信息

Xu Jinhuan, Ming Xi, Wang Chunyan, Xu Bi, Xiao Yi

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R.China.

出版信息

Medicine (Baltimore). 2021 May 7;100(18):e25784. doi: 10.1097/MD.0000000000025784.

Abstract

INTRODUCTION

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.

PATIENT CONCERNS

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.

DIAGNOSIS

Both patients were diagnosed with RRMM according to the International Myeloma Working Group criteria.

INTERVENTIONS

Both patients received infusions of anti-BCMA CAR-T cells following an induction chemotherapy regimen of cyclophosphamide and fludarabine.

OUTCOMES

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.

CONCLUSIONS

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.

TRIAL REGISTRATION

ChiCTR-OPC-16009113.

摘要

引言

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。

患者情况

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。

诊断

根据国际骨髓瘤工作组标准,两名患者均被诊断为RRMM。

干预措施

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。

结果

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。

结论

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。

试验注册

ChiCTR-OPC-16009113。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ee/8104258/01371cd01a7c/medi-100-e25784-g001.jpg

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