改良R^(2)方案治疗初治或复发难治性老年B细胞非霍奇金淋巴瘤的临床疗效和安全性

Combination of lenalidomide and rituximab in treatment of the elderly patients with initially treated or relapsed and refractory B-cell non-Hodgkin’s lymphoma:clinical efficacy and safety

目的:评估改良来那度胺与利妥昔单抗联合(改良R^(2)方案)治疗初治或复发难治性B细胞非霍奇金淋巴瘤(B-cell non-Hodgkin’s lymphoma,B-NHL)老年患者的疗效和安全性。方法:研究对象为2018年1月—2020年9月接受治疗的25例年龄≥65岁的初治或复发难治性B-NHL老年患者,均接受改良R^(2)方案治疗(来那度胺25 mg/d口服第1~14天,停7 d;利妥昔单抗第1天375 mg/m^(2)静脉滴注;每21 d为1个疗程)。每2个疗程评价近期疗效,对达到完全缓解和部分缓解的患者继续给予改良R^(2)方案治疗,总疗程数为6~8个。如果6~8个疗程后达到完全缓解,则每3个月进行复查。对于达到完全缓解或部分缓解的复发难治性患者(FL患者除外),单用来那度胺维持治疗2年或直至疾病进展。结果:25例患者中,6例为初治患者,19例为复发难治性患者。6例(24.0%)达到完全缓解,其中初治患者4例(4/6,66.7%)、复发难治性患者2例(2/19,10.5%),初治患者的完全缓解率高于复发难治性患者(P<0.01);11例(44.0%)达到部分缓解;3例(12.0%)为疾病稳定;5例(20.0%)为疾病进展。DLBCL(11例)、FL(9例)和MCL(5例)患者的客观缓解率分别为45.6%、88.9%和80.0%。所有患者的客观缓解率为68.0%(17/25)。中位随访期为14个月,1年无进展生存率为56%(95%置信区间:38%~71%),1年总生存率为72%(95%置信区间:56%~82%)。主要不良反应为血液学不良反应以及皮疹伴瘙痒,其中Ⅲ~Ⅳ级中性粒细胞减少发生率为36.0%(9/25),Ⅲ~Ⅳ级血小板减少发生率为8.0%(2/25),Ⅳ级贫血发生率为14%(1/25),皮疹伴瘙痒发生率为20.0%(5/25)。其他不良反应包括乏力(72.0%)、轻度血栓(16.0%)以及间质性肺炎(8.0%)。未发生治疗相关性死亡。结论:改良R^(2)方案治疗初治或复发难治性B-NHL具有较高的反应性以及良好的耐受性。

Objective:To evaluate the efficacy and safety of modified lenalidomide combined with rituximab(modified R^(2)regimen)in the treatment of initially treated or relapsed and refractory B-cell non-Hodgkin’s lymphoma(B-NHL)in elderly patients.Methods:The study subjects were 25 elderly patients aged≥65 years with initially treated or relapsed and refractory B-NHL who received treatment from January 2018 to September 2020.All of the patients received modified R^(2)regimen(lenalidomide 25 mg/d was taken orally d1-14;rituximab 375 mg/m^(2)was given intravenously d1;repeated every 21 days).The short-term response was evaluated every 2 courses of treatment,and the patients who achieved complete remission and partial remission were continued to be treated with modified R^(2)regimen,with a total of 6-8 courses of treatment.If complete remission was achieved after 6-8 courses of treatment,recheck every 3 months.For relapsed and refractory patients(except patients with follicular lymphoma)who achieved complete or partial remission,they would be treated with lenalidomide alone for 2 years or until the disease progresses.Results:Of the 25 patients,6 were initially treated and 19 were relapsed and refractory.Complete remission was achieved in 6 patients(24.0%),of which 4 patients were initially treated(4/6,66.7%)and 2 patients were relapsed and refractory(2/19,10.5%).The complete remission rate of initially treated patients was higher than that of the relapsed and refractory patients(P<0.01);11 patients(44.0%)achieved partial remission;3 patients(12.0%)had stable disease;5 patients(20.0%)had progressive disease.The objective response rates(ORRs)of patients with diffuse large B-Cell lymphoma(DLBCL)(n=11),follicular lymphoma(FL)(n=9)and mantle cell lymphoma(MCL)(n=5)were 45.6%,88.9%and 80.0%,respectively.The ORR of all patients was 68.0%(17/25).The median follow-up period was 14 months.The 1-year progression-free survival rate was 56%(95%confidence interval:38%-71%),and the 1-year overall survival rate was 72%(95%confidence interval:56%-82%).The main adverse reactions were hematological adverse reactions and rash with pruritus.The incidence of grade III-IV neutropenia was 36.0%(9/25),the incidence of grade III-IV thrombocytopenia was 8.0%(2/25),the incidence of grade IV anemia was 14%(1/25),and the incidence of rash with pruritus was 20.0%(5/25).Other adverse reactions included fatigue(72.0%),mild thrombosis(16.0%)and interstitial pneumonia(8.0%).No treatmentrelated deaths occurred.Conclusion:The modified R^(2)regimen has high reactivity and good tolerance in the treatment of initially treated or relapsed and refractory B-NHL in elderly patients.