来那度胺联合静脉利妥昔单抗（REVRI）治疗复发/难治性原发性中枢神经系统淋巴瘤或原发性眼内淋巴瘤：法国眼脑淋巴瘤（LOC）网络和淋巴瘤研究协会（LYSA）的多中心前瞻性“概念验证”二期研究†。
Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)†.
机构信息
Department of Hematology, Centre Hospitalier Lyon Sud, Université Claude Bernard Lyon 1, Pierre-Bénite; Department of Hematology, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon.
Departments of Biostatistics, Aix Marseille University, AP-HM, Marseille.
出版信息
Ann Oncol. 2019 Apr 1;30(4):621-628. doi: 10.1093/annonc/mdz032.
BACKGROUND
Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R2) in DLBCL-PCNSL.
PATIENTS AND METHODS
Patients with refractory/relapsed (R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R2 (rituximab 375/m2 i.v. D1; lenalidomide 20 mg/day, D1-21 for cycle 1; and 25 mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point was the overall response rate (ORR) at the end of induction (P0 = 10%; P1 = 30%).
RESULTS
Fifty patients were included. Forty-five patients (PCNSL, N = 34; PVRL, N = 11) were assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable patients and 32.0% (95% CI 21.9-51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2 months (range 1.5-31), the median progression-free survival (PFS) and overall survival (OS) were 7.8 months (95% CI 3.9-11.3) and 17.7 months (95% CI 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS [median PFS = 9.5 months (95% CI, 8.1-14.8] for CD4/CD8 ≥ 1.6; median PFS = 2.8 months, [95% CI, 1.1-7.8) for CD4/CD8 < 1.6, P = 0.03).
CONCLUSIONS
The R2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R2 combined with methotrexate-based chemotherapy as a first-line treatment of PCNSL.
CLINICAL TRIALS NUMBER
NCT01956695.
背景
原发性中枢神经系统淋巴瘤（PCNSL）主要为非生发中心 B 细胞（non-GCB）型弥漫性大 B 细胞淋巴瘤（DLBCL）。本研究旨在确定利妥昔单抗联合来那度胺（R2）在 DLBCL-PCNSL 中的疗效。
患者和方法
本前瞻性 II 期研究纳入了难治/复发（R/R）DLBCL-PCNSL 或原发性眼内淋巴瘤（PVRL）患者。诱导治疗包括 8 个 28 天周期的 R2（利妥昔单抗 375/m2，静脉注射 D1；来那度胺 20mg/天，第 1-21 天用于第 1 个周期；第 2-21 天用于后续周期；25mg/天）；在有反应的患者中，诱导治疗后进行 12 个 28 天周期的来那度胺维持治疗（10mg/天，第 1-21 天）。主要终点是诱导治疗结束时的总缓解率（ORR；P0=10%；P1=30%）。
结果
共纳入 50 例患者。45 例患者（PCNSL，n=34；PVRL，n=11）可评估疗效。在可评估患者中，诱导治疗结束时的 ORR 为 35.6%（95%CI 21.9-51.2），意向治疗分析中的 ORR 为 32.0%（95%CI 21.9-51.2），包括 13 例完全缓解（CR）/未确认的 CR（uCR；29%）和 3 例部分缓解（PR；7%）。最佳反应是在诱导治疗期间获得 18 例 CR/uCR（40%）和 12 例 PR（27%）。18 例和 5 例患者分别开始和完成了维持治疗阶段。中位随访时间为 19.2 个月（范围 1.5-31），中位无进展生存期（PFS）和总生存期（OS）分别为 7.8 个月（95%CI 3.9-11.3）和 17.7 个月（95%CI 12.9-NR）。未观察到意外毒性。外周血 CD4/CD8 基线比值影响 PFS[CD4/CD8≥1.6 时中位 PFS=9.5 个月（95%CI，8.1-14.8）；CD4/CD8<1.6 时中位 PFS=2.8 个月（95%CI，1.1-7.8），P=0.03]。
结论
R2 方案在 R/R PCNSL 和 PVRL 患者中显示出显著的活性。这些结果支持评估 R2 联合甲氨蝶呤为基础的化疗作为 PCNSL 一线治疗的疗效。
临床试验注册号
NCT01956695。
Zotero 插件