Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma.

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-04-11 DOI:10.1016/j.clml.2025.04.004

Chaitra Ujjani, Hongkun Wang, Catherine Broome, Ajay K Gopal, Stephen D Smith, Catherine Lai, Mazyar Shadman, Lori Leslie, Edus H Warren, Ryan Lynch, Nicole Swanson, Trenton Grossfeld, Bruce D Cheson, Kieron Dunleavy

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引用次数: 0

Abstract

Background: Bruton tyrosine kinase (BTK) inhibitors are approved in several B-cell malignancies, including the recent authorization of zanubrutinib for relapsed or refractory follicular lymphoma (FL).

Methods: Based on preclinical studies demonstrating synergy with ibrutinib and the B-cell lymphoma (BCL)-2 inhibitor, venetoclax, in FL cell lines, we conducted a multicenter phase Ib/II study evaluating this combination in relapsed or refractory FL.

Results: The recommended phase 2 dose was ibrutinib 560 mg and venetoclax 600 mg. There was no evidence of clinical tumor lysis syndrome, despite the omission of a venetoclax ramp up. At a median duration of therapy of 6 months, the most common adverse events were low grade diarrhea (83%), infection (75%), and rash (58%). Amongst the 24 patients enrolled, the overall and complete response (CR) rates were 63% and 21%. At a median follow up of 6.9 months, the median progression-free survival was 8.2 months, and the median duration of CR (n = 5) was 38 months.

Conclusion: The combination of a BTK and BCL2 inhibitor is efficacious in relapsed/refractory FL and represents a unique dual-targeted approach warranting further investigation.

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伊鲁替尼和Venetoclax治疗复发和难治性滤泡性淋巴瘤。

背景：布鲁顿酪氨酸激酶（BTK）抑制剂已被批准用于治疗多种b细胞恶性肿瘤，包括最近批准的zanubrutinib用于治疗复发或难治性滤泡性淋巴瘤（FL）。方法：基于临床前研究表明伊鲁替尼和b细胞淋巴瘤(BCL)-2抑制剂venetoclax在FL细胞系中的协同作用，我们进行了一项多中心Ib/II期研究，评估该联合治疗复发或难治性FL的效果。结果：推荐的2期剂量为伊鲁替尼560 mg和venetoclax 600 mg。没有临床肿瘤溶解综合征的证据，尽管遗漏了venetoclax斜坡。在治疗的中位持续时间为6个月时，最常见的不良事件是低度腹泻（83%）、感染（75%）和皮疹（58%）。在入选的24例患者中，总缓解率和完全缓解率分别为63%和21%。中位随访时间为6.9个月，中位无进展生存期为8.2个月，中位CR持续时间（n = 5）为38个月。结论：BTK和BCL2抑制剂联合治疗复发/难治性FL有效，是一种独特的双靶点治疗方法，值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Lymphoma, Myeloma & Leukemia ONCOLOGY-HEMATOLOGY

CiteScore

2.70

自引率

3.70%

发文量

1606

审稿时长

26 days

期刊介绍： Clinical Lymphoma, Myeloma & Leukemia is a peer-reviewed monthly journal that publishes original articles describing various aspects of clinical and translational research of lymphoma, myeloma and leukemia. Clinical Lymphoma, Myeloma & Leukemia is devoted to articles on detection, diagnosis, prevention, and treatment of lymphoma, myeloma, leukemia and related disorders including macroglobulinemia, amyloidosis, and plasma-cell dyscrasias. The main emphasis is on recent scientific developments in all areas related to lymphoma, myeloma and leukemia. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.