伊布替尼、利妥昔单抗和来那度胺用于 75 岁或以上初治弥漫性大 B 细胞淋巴瘤不适合或虚弱患者：一项 2 期、单臂研究。

Ibrutinib, rituximab, and lenalidomide in unfit or frail patients aged 75 years or older with de novo diffuse large B-cell lymphoma: a phase 2, single-arm study.

机构信息

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Lancet Healthy Longev. 2022 Jul;3(7):e481-e490. doi: 10.1016/S2666-7568(22)00123-4.

DOI:10.1016/S2666-7568(22)00123-4

PMID:36102758

Abstract

BACKGROUND

The optimal treatment for older adults with diffuse large B-cell lymphoma (DLBCL) needs to be further explored due to patient comorbidities, standard immunochemotherapy intolerance, and unfavourable genetic features. We did a phase 2 trial of ibrutinib, rituximab, and lenalidomide (iR2) to evaluate the efficacy and safety in older adult patients with de novo DLBCL.

METHODS

In this phase 2, single-arm study, unfit or frail patients with de novo DLBCL aged 75 years or older were enrolled at Shanghai Ruijin Hospital, Shanghai, China. During the induction phase from cycle 1 to 6, 560 mg ibrutinib was given orally daily throughout each 21-day treatment cycle, 375 mg/m rituximab was given intravenously on day 1, and 25 mg lenalidomide was given orally daily from day 1 to 10 in each cycle. Patients who had a complete response after induction were given another 6 cycles of lenalidomide maintenance (25 mg orally daily from day 1 to 10 every 21 days from cycle 7 to 12). The primary endpoint was complete response rate after 6 cycles or at the end of the induction treatment. This trial is registered with ClinicalTrials.gov, NCT03949062.

FINDINGS

Between May 15, 2019, and May 8, 2020, a total of 30 patients were enrolled. The end of induction complete response rate was 56·7% (95% CI 37·4-74·5), and overall response rate was 66·7% (95% CI 47·2-82·7). With a median follow-up of 27·6 months (IQR 23·9-29·6), the 2-year progression-free survival rate was 53·3% (95% CI 34·3-69·1) and the 2-year overall survival rate was 66·7% (95% CI 46·9-80·5). The main grade 3-4 haematological adverse events were neutropenia (seven patients [23%]), thrombocytopenia (three patients [10%]), and anaemia (two patients [7%]). The most common grade 3-4 non-haematological adverse event was pulmonary infection (seven patients [23%]). Atrial fibrillation was observed in three (10%) patients, including one grade 2 and two grade 3.

INTERPRETATION

A chemotherapy-free iR2 regimen is clinically effective and safe and warrants further investigation in phase 3 trials as first-line treatment in older adult patients with DLBCL.

FUNDING

National Natural Science Foundation of China, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Clinical Research Plan of Shanghai Hospital Development Center, and Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine.

摘要

背景

由于患者合并症、标准免疫化疗不耐受和不利的遗传特征，需要进一步探索治疗老年弥漫性大 B 细胞淋巴瘤（DLBCL）的最佳方法。我们进行了一项关于伊布替尼、利妥昔单抗和来那度胺（iR2）的 2 期临床试验，以评估该方案在初治 DLBCL 老年患者中的疗效和安全性。

方法

在这项中国上海瑞金医院进行的 2 期、单臂研究中，纳入了年龄 75 岁及以上、初治、不适合或虚弱的 DLBCL 患者。在诱导治疗阶段（第 1 周期至第 6 周期），每天给予 ibrutinib 560mg 口服，每 21 天一个周期；第 1 天给予 375mg/m2 的利妥昔单抗静脉滴注；每个周期的第 1 天至第 10 天给予来那度胺 25mg 口服。诱导治疗后达到完全缓解的患者接受另外 6 个周期的来那度胺维持治疗（从第 7 周期至第 12 周期，每 21 天一个周期，第 1 天至第 10 天给予来那度胺 25mg 口服）。主要终点为 6 个周期或诱导治疗结束后的完全缓解率。该试验在 ClinicalTrials.gov 注册，编号为 NCT03949062。

结果

2019 年 5 月 15 日至 2020 年 5 月 8 日期间，共纳入 30 例患者。诱导治疗结束时的完全缓解率为 56.7%（95%CI，37.4-74.5），总缓解率为 66.7%（95%CI，47.2-82.7）。中位随访 27.6 个月（IQR，23.9-29.6）时，2 年无进展生存率为 53.3%（95%CI，34.3-69.1），2 年总生存率为 66.7%（95%CI，46.9-80.5）。主要的 3-4 级血液学不良事件为中性粒细胞减少症（7 例[23%]）、血小板减少症（3 例[10%]）和贫血（2 例[7%]）。最常见的 3-4 级非血液学不良事件是肺部感染（7 例[23%]）。有 3 例（10%）患者发生房颤，包括 1 例 2 级和 2 例 3 级。