奥布替尼联合利妥昔单抗及大剂量甲氨蝶呤治疗初治原发中枢神经系统淋巴瘤的疗效分析

Orelabrutinib,rituximab and high-dose methotrexate for newly diagnosed primary central nervous system lymphoma:a retrospective analysis on efficacy and safety

目的通过回顾性研究分析奥布替尼联合利妥昔单抗及大剂量甲氨蝶呤(RMO方案)治疗新诊断原发中枢神经系统淋巴瘤(PCNSL)患者的临床疗效和安全性。方法收集2021年1月—2023年1月在我院治疗的初治PCNSL患者资料。所有患者均接受RMO方案治疗:奥布替尼片150 mg口服,1次/d,d1~21;利妥昔单抗375mg·m^(-2)静脉滴注,d1;甲氨蝶呤注射液3.5 g·m^(-2)静脉滴注3 h,d2;21 d为1个治疗周期。所有患者均治疗6个周期,每2个周期后进行疗效评估,6个周期治疗结束后行PET-CT及脑核磁评估疗效。治疗结束后,符合移植条件者行自体造血干细胞移植巩固治疗,有条件者进行奥布替尼维持治疗。观察患者的临床疗效及不良反应。结果共纳入12例患者,中位年龄58(45~74)岁,病理类型均为CD20阳性弥漫大B细胞淋巴瘤。治疗4个周期后疗效评估为完全缓解(CR)4例、部分缓解(PR)7例、疾病进展(PD)1例,CR率为33.3%,客观缓解率(ORR)为91.7%。治疗6个周期后疗效评估为CR 8例、PR 2例、PD 2例,CR率为66.6%,ORR为83.3%。中位无进展生存期(mPFS)未达到,中位总生存期(mOS)未达到,6个月PFS率为83.3%,6个月OS率为100%,12个月PFS率为64.8%,12个月OS率为80.8%。有8例患者接受基因突变检测,其中MCD型7例、A53型1例。7例MCD型患者接受治疗后ORR为100%,CRR为85.7%。主要不良反应为疲劳(25.0%),仅有1例不良反应≥3级,最常见的血液学毒性为白细胞减少(16.7%),所有患者均未发生房颤及肾功能衰竭。结论RMO方案对于初治PCNSL患者是安全、有效的治疗方案。

Objective To retrospectively analyze the clinical efficacy and safety of the combination of orelabrutinib,rituximab and high-dose methotrexate(RMO)regimen in the treatment of newly diagnosed primary central nervous system lymphoma(PCNSL)patients.Methods The data of PCNSL patients treated in our hospital between January 2021 and January 2023 were analyzed retrospectively.All patients received 6 cycles of RMO regimen(rituximab 375 mg·m^(-2),iv,d1;orelabrutinib 150 mg,qd,po,d1~21;methotrexate 3.5 g·m^(-2),iv,d2;3 weeks per cycle)as the induction therapy.Efficacy was assessed by MRI/PET every 2 cycles.After 6 cycles of RMO induction therapy,patients who achieved CR/CRu/PR by MRI and PET received autologous peripheral blood hematopoietic stem cell transplantation as consolidation therapy.Orelabrutinib monotherapy was prescribed as maintenance therapy until the disease progresses.The primary endpoint was the safety and efficacy of this regimen in newly diagnosed PCNSL patients.Results A total of 12 patients were enrolled in this study.The median age of the 12 patients was 58(45~74)years old.All the patients were pathologically diagnosed as CD20-positive diffuse large B-cell lymphoma(DLBCL).After 4 cycles of RMO therapy,the efficacy was evaluated as complete response(CR)in 4 cases,partial response(PR)in 7 cases,and progressive disease(PD)in 1 case.The objective response rate(ORR)was 91.7%,and the CR rate was 33.3%.After 6 cycles of treatment,the efficacy was evaluated as 8 cases of CR,2 cases of PR,and 2 cases of PD.The ORR was 83.3%,and the CR rate was 66.6%.The median progression-free survival(mPFS)and the median overall survival(mOS)were not achieved.The 6-month PFS rate was 83.3%,the 6-month OS rate was 100%,the 12-month PFS rate was 64.8%,and the 12-month OS rate was 80.8%.Eight patients underwent gene mutation testing,including 7 cases of MCD type and 1 case of A53 type.After receiving this regimen,the ORR and CR rate of 7 patients with MCD type were 100%and 85.7%,respectively.The main adverse events of RMO regimen was fatigue(25%),and only one patient had≥3 grade adverse reaction.The most common hematologic toxicity was leukopenia(16.7%),and none of the patients experienced atrial fibrillation and renal failure.Conclusion The RMO regimen is a safe and effective treatment option for newly diagnosed PCNSL patients.