Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma
- PMID: 40340130
- DOI: 10.1016/j.clml.2025.04.004
Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma
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.
Keywords: BCL2 inhibitor; BTK inhibitor; Follicular lymphoma; Ibrutinib; Venetoclax.
Copyright © 2025 Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosure Chaitra Ujjani: Consultancy: AbbVie, Janssen, Genentech, Beigene, Astrazeneca, Lilly, Bristol Myer Squibb, Genmab, Genentech, Allogene, Atara, ADC Therapeutics. Research: Lilly, AbbVie, Pharmacyclics, Astrazeneca, Kite Mazyar Shadman: Consultancy: Abbvie, Genentech, AstraZeneca, Genmab, Janssen, Beigene, Bristol Myers Squibb, Morphosys/Incyte, Kite Pharma, Eli Lilly, Fate therapeutics, Nurix and Merck. Research funding: Mustang Bio, Genentech, AbbVie, Beigene, AstraZeneca, Genmab, Morphosys/Incyte and Vincerx; Stock options: Koi Biotherapeutics. Employment: Bristol Myers Squibb (spouse) Ajay K Gopal: Research Funding: Merck, I-Mab bio, IgM Bio, Takeda, Gilead, Astra-Zeneca, Agios, Janssen, BMS, SeaGen, Teva, Genmab, Beigene. Consultancy/Honoraria: Incyte, Kite, Morphosys/Incyte, ADCT, Acrotech, Merck, Karyopharm, Servier, Beigene, Cellectar, Janssen, Compliment, SeaGen, Epizyme, I-Mab bio, Gilead, Genentech, Lilly, Caribou, Fresenius-Kabi, Scitek, Sana; Stock Options: Compliment Corporation Lori Leslie: Consultancy: TG therapeutics, Seagen, Pharmacyclics, Merck, Janssen, Epizyme, Lilly, Beigene, ADC Therapeutics, Astrazeneca, Genmab, Abbvie, Kite; Speakers Bureau TG therapeutics, Seagen, Pharmacyclics, Janssen, Epizyme Lilly, Beigene, Genmab, Abbvie, Kite Bruce Cheson: Consultancy: Beigene, Abbvie, Lilly, Symbio, Speakers Bureau: Beigene, Incyte, Lilly. Research funding: Genentech, Genmab, Lilly, Beigene, Prelude, Morphosys/Incyte Stephen D Smith: Research funding: ADC Therapeutics, Astrazeneca, Ayala (spouse), Bayer, Beigene, Bristol Myers Squibb (spouse), De Novo Biopharma, Enterome, Genentech, Ignyta (spouse), Incyte Corporation, Kymera Therapeutics, Merck Sharp and Dohme Corp, MorphoSys, Nanjing Pharmaceuticals Co., Ltd., Viracta Therapeutics; Consultancy: Beigene, Kite pharma, Lumanity, Merck Ryan Lynch: Research Funding: TG Therapeutics, Incyte, Bayer, Cyteir, Genentech, SeaGen, Rapt, Merck, Janssen. Consultancy/Honoraria: SeaGen, Foresight Diagnostics, Abbvie, Janssen, Merck Kieron Dunleavy: Consultancy: Genentech, Pharmacyclics, Abbvie. Research funding: Genentech, Abbvie, Pharmacyclics Hongkun Wang, Catherine Broome, Catherine Lai, Edus Warren, Nicole Swanson, and Trenton Grossfeld have no relevant conflicts to declare.
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