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. 2025 Sep;25(9):e663-e667.
doi: 10.1016/j.clml.2025.05.011. Epub 2025 May 16.

Feasibility of Bruton's Tyrosine Kinase Inhibitor Discontinuation in Chronic Lymphocytic Leukemia: The Patient Perspective

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Feasibility of Bruton's Tyrosine Kinase Inhibitor Discontinuation in Chronic Lymphocytic Leukemia: The Patient Perspective

Deborah M Stephens et al. Clin Lymphoma Myeloma Leuk. 2025 Sep.

Abstract

Background: Bruton's tyrosine kinase inhibitors (BTKi) have prolonged survival in chronic lymphocytic leukemia (CLL), however continuous administration increases toxicity. Little is known about clinical outcomes of patients who discontinue BTKi for reasons other than CLL progression. We aimed to report these outcomes.

Patients/methods: With the CLL Society, we solicited volunteers with CLL who self-reported BTKi discontinuation for reasons other than CLL progression to participate in a web-based survey.

Results: In 170 patients, BTKi was discontinued for toxicity, because CLL was in remission, or personal choice in 62%, 14% and 8%, respectively. When asked how they felt about stopping the BTKi, most were relieved that they may eliminate toxicity (45%), could focus less on CLL (11%), and would not have to pay for the medicine (7%), while 29% experienced anxiety. A statistically significant increase in perceived quality of life (QOL) was observed from prior- versus post-BTKi discontinuation. Of patients who reported that they experienced clinical CLL progression (n = 80), 46% reported that these events did not happen for ≥ 1 year after BTKi discontinuation. Those that were on a BTKi for ≥ 2 years before discontinuation had more time without CLL relapse.

Conclusions: These data provide a unique report of patient experiences. The data suggest that BTKi may be feasible and result in a period of treatment-free remission. The data also indicate that patients are generally relieved when they anticipate BTKi discontinuation and observe significant QOL improvements after BTKi discontinuation. As such, these data should prompt prospective study of time-limited BTKi therapy for CLL.

Keywords: Acalabrutinib; Drug holiday; Ibrutinib; Treatment discontinuation; Zanubrutinib.

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Conflict of interest statement

Disclosure DMS: Consulting for Abbvie, AstraZeneca, Beigene, BMS, Celegene, Eli Lilly,Genentech, Janssen, Pharmacyclics. Research funding from Abbvie, Genentech, Beigene. CS: Gallup (Retired); Current equity holder in publicly traded company: Eli Lilly, Johnson & Johnson, Kenvue, Novartis, Pacific Biosciences of California, Dr. Reddy’s Laboratories Limited. CC: Honoraria and consulting for AbbVie, Allogene, AstraZeneca, Beigene, Genentech, Janssen, Lilly, MEI Pharma, Mingsight, Octapharma, TG Therapeutics, have served on speaker’s bureaus for AbbVie, AstraZeneca, Beigene, Genentech, Lilly. Stock ownership in Bluebird Bio, Geron, Pfizer. Research funding (paid to my institution) from AbbVie, AstraZeneca, Beigene, CarnaBio, Lilly. AD: Consulting for AstraZeneca, Abbvie, Beigene, Genentech, Nurix, MorphoSys, Incyte, TG Therapeutics, Bayer, ADCT, BMS, GenMab, Janssen. Research funding from AstraZeneca, Nurix, TG Therapeutics, Bayer, Takeda, MEI Pharma, BMS, and GenMab. BH: Consulting, honoraria and research funding from Regeneron, Beigene, Pharmacyclics, BMS, Abbvie, AstraZeneca, Seattle Genetics, Genentech, Gilead. MS: Consulting, advisory boards, steering committees or data safety monitoring committees: 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. AG: Honoraria from AstraZeneca, Beigene, Janssen, Lilly, Celgene. Research funding from AstraZeneca, Beigene, Janssen, Lilly. MH: Consulting: ADC, Janssen, Pharmacyclics, BeiGene, Novartis, Astra-Zeneca, Abbvie, Kite, TG. Research Funding: Genentech. Travel: BMS AW: Consulting ADC Therapeutics, AstraZeneca, BTG Pharmaceuticals, BeiGene. DE: Consulting Beigene, ADC therapeutics, Speaking AstraZeneca. PB: Consulting from Abbvie, AstraZeneca, TG Therapeutics, BMS, Clegene, Genentech, Gilead, MEI Pharma, Janssen, Merck, Pharmacyclics, MorphoSys, Seattle Genetics. Research funding from AstraZeneca and TG Therapeutics. SO: Consulting from Abbvie, AstraZeneca, Autolus, Beigene, BMS, Lilly, GlaxoSmithKline, Janssen, Johnson and Johnson, Merck, Pfizer, Pharmacyclics, TG Therapeutics, Vaniam Group. Research funding from alliance, AstraZeneca, Caribou, Gilead, Kite, Mustang Bio, Nurix, Pfizer, Pharmacyclics, Regeneron, TG Therapeutics. BK: Equity in Abbvie, AstraZeneca, BMEA, BMS, Invyvid, Johnson and Johnson, Merck, Nurix, Pfizer, Vincerix. Consulting for Abbvie, Beigene, BMEA, BMS, Johnson and Johnson, Lilly. Honoraria from AstraZeneca, BMS, GenMab, Invivyd. JCB: Equity in Vincerx Pharma, Eilean Therapeutics, and Kurome Therapeutics; Consultant: Abbvie, AstraZeneca, and Syndax.

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