来那度胺联合硼替佐米和地塞米松诱导治疗初诊多发性骨髓瘤患者的疗效和安全性

Efficacy and safety of lenalidomide combined with bortezomib and dexamethasone induction therapy in newly diagnosed patients with multiple myeloma

目的评估来那度胺联合硼替佐米和地塞米松(VRD)治疗初诊多发性骨髓瘤(MM)患者的疗效和安全性。方法回顾性分析自2018年11月至2021年2月在苏州大学附属第一医院诊断并接受VRD方案诱导治疗的150例初诊MM患者,评价初诊MM患者应用VRD方案诱导治疗的疗效及安全性。结果中位随访时间22(1~38)个月,2例(1.3%)患者治疗早期死亡,148例(98.7%)完成诱导治疗。116例(77.3%)患者动员采集自体造血干细胞,采集物合格者101例(87.1%),其中采集物优秀者48例(41.4%)。3年无进展生存(PFS)率为59%,3年总生存(OS)率为83%。诱导治疗后完全缓解/严格意义的完全缓解率为54.4%,≥非常好的部分缓解率为77.3%,总体反应率为86.0%,微小残留病阴性率为46.0%。细胞遗传学高危患者的疗效与标危患者相比差异无统计学意义(P=0.456),遗传学高危患者的中位PFS时间较标危患者缩短(33个月对未达到,P=0.014),中位OS时间的差异无统计学意义(均未达到,P=0.072)。血液学不良事件中血小板减少发生率最高(72%),其次为中性粒细胞减少(42%)和贫血(20%)。非血液学不良事件中周围神经炎发生率最高(56.7%);消化道症状主要为便秘(30.0%)和腹泻(17.3%);感染主要为上呼吸道感染(23.3%)和肺部感染(7.3%);转氨酶升高发生率较高(32.6%)。与肾功能正常患者相比,初诊时肾功能不全患者血小板减少(90.0%对63.7%,P=0.001)、贫血(33.3%对13.7%,P=0.005)、中性粒细胞减少(54.2%对36.3%,P=0.038)、腹泻(27.1%对12.7%,P=0.030)、肢体水肿(20.8%对3.9%,P=0.030)、发热(20.8%对4.9%,P=0.006)、血栓(8.3%对0,P=0.016)、肾功能恶化(20.8%对3.9%,P=0.030)的发生率较高。结论VRD方案治疗初诊MM疗效显著,不影响造血干细胞采集,不良事件可控,但肾功能不全患者不良事件发生率较高。

Objective This study aimed to evaluate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone(VRD)in the treatment of newly diagnosed multiple myeloma(MM).Methods A total of 150 newly diagnosed patients with MM diagnosed in The First Affiliated Hospital of Soochow University from November 2018 to February 2021 and received VRD as the induction regimen were included to evaluate the safety and efficacy of VRD induction therapy for newly diagnosed MM.Results The median follow-up was 22 months,two patients(1.3%)died early after treatment,and 148 patients(98.7%)completed induction therapy.116 patients(77.3%)were mobilized to collect autologous hematopoietic stem cells,101 cases(87.1%)were qualified in the collection,of which 48 cases(41.4%)were excellent in the collection.The 3-year progression-free survival(PFS)rate was 59%,and the 3-year overall survival(OS)rate was 83%.After induction,complete remission(CR)/stringent CR rate was 54.4%,≥very good partial remission rate was 77.3%,overall response rate was 86.0%,and minimal residual disease negative rate was 46.0%.There was no statistically significant difference in the efficacy of cytogenetic high-risk patients compared with standard risk patients(P=0.456).The median PFS time of cytogenetic high-risk patients was shorter than that of standard risk patients(not reached vs 33 months,P=0.014).There was no statistically significant difference in the median OS time(not reached vs not reached,P=0.072).The highest incidence of hematological adverse events was thrombocytopenia(72%),followed by neutropenia(42%)and anemia(20%).The highest incidence of non-hematological adverse events was peripheral neuritis(56.7%).The main digestive tract symptoms include constipation(30.0%)and diarrhea(17.3%).Upper respiratory tract infection(23.3%)and lung infection(7.3%)are the main infections.The incidence of adverse thrombocytopenia(90.0%vs 63.7%,P=0.001),neutropenia(54.2%vs 36.3%,P=0.038),anemia(33.3%vs 13.7%,P=0.005),diarrhea(27.1%vs 12.7%,P=0.030),limb edema(20.8%vs 3.9%,P=0.030),fever(20.8%vs 4.9%,P=0.006),thrombosis(8.3%vs 0,P=0.016),and renal function deterioration(20.8%vs 3.9%,P=0.030)in patients with renal insufficiency was higher than that in patients with normal renal function.Conclusion The VRD regimen has a significant effect on newly diagnosed MM,does not affect the hematopoietic stem cell collection,and has controllable adverse events;however,the incidence of adverse events was higher in patients with renal insufficiency.