伊沙佐米、来那度胺、地塞米松治疗复发/难治多发性骨髓瘤的疗效与安全性分析:一项国内多中心真实世界研究

The efficacy and safety profile of ixazomib/lenalidomide/dexamethasone in relapsed/refractory multiple myeloma:a multicenter real-world study in China

目的评估伊沙佐米、来那度胺、地塞米松(IRd)方案治疗复发/难治多发性骨髓瘤(MM)的疗效及安全性。方法纳入2018年7月至2020年5月于国内14个中心接受至少1个周期IRd方案治疗的复发/难治MM患者。除7例起始剂量作调整的患者以外,其余患者伊沙佐米起始剂量为4 mg。来那度胺剂量根据患者肌酐清除率进行调整。每周期进行疗效及安全性评估。结果共纳入74例患者,中位年龄65岁,11例(14.9%)患者曾接受>三线治疗。总体反应率(ORR)为54.1%(40/74),其中7例(9.5%)达严格意义的完全缓解或完全缓解,14例(18.9%)达非常好的部分缓解,19例(25.7%)达部分缓解,中位无进展生存时间为9.9月,中位总生存时间为20个月,中位获得反应时间为1个月。总体疗效与生存结果与TOURMALINE-MM1中国延展性研究(TOURMALINE-MM1 CCS)相近。硼替佐米难治、来那度胺难治、两药均难治患者的ORR分别为52.0%(13/25)、57.1%(4/7)和33.3%(6/18)。3~4级不良事件(AE)发生率为36.5%(27/74)。主要血液学不良反应为贫血、血小板减少、淋巴细胞减少及中性粒细胞减少。主要非血液学不良反应为乏力、消化道症状及感染。2例患者出现3级周围神经病变。与不符合TOURMALINE-MM1 CCS试验入组标准的患者相比,符合入组标准的患者ORR更高[77.8%(14/18)对46.4%(26/56),P=0.020],两组3~4级AE发生率的差异无统计学意义[33.3%(6/18)对37.5%(21/56),P=0.749]。结论IRd方案治疗复发/难治MM具有较好的疗效及安全性。

Objective To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone(IRd)in Chinese patients with relapsed/refractory multiple myeloma(MM).Methods This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least.Ixazomib at an initial oral dose of 4 mg was administered.Seven patients had dose adjustment to 3 mg at the time of first dose.The lenalidomide doses were adjusted according to creatinine clearance rate.The efficacy and safety were evaluated every cycle.Results In the study cohort of 74 patients,the median age was 65 years and 11(14.9%)patients received over three lines of therapy.Overall response rate(ORR)was 54.1%(40/74),and 7(9.5%),14(18.9%),and 19(25.7%)patients achieved stringent complete response or complete response,very good partial response,and partial response,respectively.The median progression-free survival and overall survival were 9.9 and 20 months,respectively.The median time to response was 1 month.The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study.The ORR of patients refractory to bortezomib,lenalidomide,and bortezomib plus lenalidomide were 52.0%(13/25),57.1%(4/7),and 33.3%(6/18),respectively.The rate of grade 3-4 adverse events was 36.5%(27/74).Common hematological toxicities were anemia,thrombocytopenia,lymphopenia,and neutropenia.Common non-hematological toxicities were fatigue,gastrointestinal symptoms,and infections.Two cases of grade 3 peripheral neuropathy were reported.The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients[77.8%(14/18)vs 46.4%(26/56),P=0.020].There was no difference in the rate of grade 3-4 adverse events[33.3%(6/18)vs 37.5%(21/56),P=0.749].Conclusion The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.