苯达莫司汀联合利妥昔单抗治疗进展期边缘区淋巴瘤的临床因素分析

Clinical features of bendamustine combined with rituximab in the treatment of advanced marginal zone lymphoma

目的:研究影响苯达莫司汀联合利妥昔单抗(BR)治疗边缘区淋巴瘤(MZL)疗效的相关临床因素和分子特征。方法:回顾性分析2020年3月—2021年9月上海交通大学医学院附属瑞金医院血液科收治的48例MZL患者的临床资料,初治患者29例,复发/进展患者19例,均应用BR方案(利妥昔单抗375 mg/m2,d0,苯达莫司汀90 mg/m2,d1~2)进行治疗。48例患者中有36例进行了DNA测序,以进一步探究基因突变对MZL患者中BR方案疗效的影响。结果:48例患者中位年龄65.5(22.0~79.0)岁,男女比例1.5:1.0。29例初治患者中,20例达完全代谢学缓解(CMR),8例达部分代谢学缓解(PMR),CMR率69.0%(20/29),总有效率(ORR)96.6%(28/29)。19例复发/进展患者中,13例达CMR,4例达PMR,CMR率68.4%(13/19),ORR 89.5%(17/19)。中位随访12(6~24)个月,初治患者1年疾病无进展生存(PFS)率为96.2%,1年总生存(OS)率为100.0%;复发/进展患者1年PFS率为100.0%,1年OS率为100.0%。进一步分析发现,MZL的起源部位[黏膜相关淋巴组织MALT淋巴瘤(胃、肺、其他)、脾边缘区淋巴瘤、结内边缘区淋巴瘤]、既往是否接受过治疗、肿块直径>7.5 cm、多个结外器官受累、骨髓受累、IPI评分3~5分、β2微球蛋白(β2-MG)升高、免疫固定电泳阳性,FISH-MALT1阳性均对患者的CMR率无显著影响(P≥0.05)。36例患者的DNA测序结果显示,其中20例(20/36,55.6%)MZL患者至少检出一个基因突变。肿瘤基因突变通路对患者的CMR率无显著影响(P≥0.05)。安全性方面,血液学不良反应以中性粒细胞减少、血小板减少和贫血为主,非血液学不良反应以恶心、呕吐和皮疹为主。结论:不论是初治还是复发/进展的MZL患者,BR方案均有确切的临床疗效,患者耐受性良好。本研究为单中心回顾性研究,还需要前瞻性大样本量的临床研究来验证。

Objective:To investigate the clinical and genetic characteristics associated with bendamustine combined with rituximab(BR)in treating marginal zone lymphoma(MZL).Methods:The clinical data of 48 MZL patients diagnosed from March 2020 to September 2021 were retrospectively evaluated,including 29 newly diagnosed patients and 19 relapsed or progressive patients.All patients were treated with BR regimen(rituximab 375 mg/m~2 d0,bendamustine 90 mg/m~2,d1-2).Targeted sequencing was applied in 36 patients to further explore the impact of genetic mutations on BR therapy in MZL patients.Results:The median age of the 48 patients was 65.5(22.0-79.0 years),and the male-to-female ratio was 1.5∶1.0.Among the 29 newly diagnosed patients,20 patients achieved complete metabolic response(CMR)and 8 patients achieved partial metabolic response(PMR),the CMR rate was 69.0%(20/29)and the overall response rate(ORR)was 96.6%(28/29).Among 19 patients with relapsed or progressive diseases,13 patients achieved CMR(68.4%,13/19),4 patients achieved PMR(21.1%,4/19),and the ORR was 89.5%(17/19).With a median follow-up of 12(6-24)months,the 1-year progression-free survival(PFS)rate and 1-year OS rate of newly diagnosed patients were 96.2%and 100.0%,respectively.The 1-year PFS rate and 1-year OS rate of relapsed or progressive patients were 100.0%.Furthermore,the subtype of MZL(MALT lymphoma[gastric,lung,others],SMZL and NMZL),prior treatment,the bulky mass,multiple extranodal involvement,bone marrow involvement,advanced IPI score,positive immunofixation electrophoresis,positive FISH-MALT1 did not exert impacts on CMR rate of patients.DNA sequencing of 36 patients showed that at least one mutation was detected in 20 MZL patients(20/36,55.6%).There was no significant relationship was observed between the oncogenic pathways enriched by tumor gene mutations and CMR in patients.BR regimen was well tolerated in MZL patients.In terms of safety,hematologic adverse events mainly included neutropenia,thrombocytopenia and anemia,while non-hematologic adverse events mainly including nausea,vomiting and rash.Conclusion:BR regimen is efficacy and tolerable in both newly diagnosed and relapsed or progressive MZL patients.This is a single center retrospective study which needs to be validated by large scale perspective clinical trial.