Ibrutinib Updates in CLL From ASH 2025

Mahesh Swaminathan, MB, MS MD Anderson Cancer Center | Vanthana Bharthi, MD MD Anderson Cancer Center

December 20, 2025

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Key Points

  • Recent data show that ibrutinib dose reductions did not compromise efficacy in patients with chronic lymphocytic leukemia (CLL).

  • Fixed-duration venetoclax-based regimens yield outcomes comparable to continuous therapy.

  • Data suggest the hazard of secondary malignancies in CLL may be increased with covalent Bruton’s tyrosine kinase (BTK) inhibitor, though time-limited regimens may avoid this risk.

Mahesh Swaminathan, MB, MS, and Vanthana Bharti, MD, both from MD Anderson Cancer Center, met at the 2025 ASH Annual Meeting (ASH 2025) to review updates on ibrutinib CLL data, including dose reductions, continuous versus fixed-duration therapy, and secondary malignancy risk.

When discussing ibrutinib dose reductions, Dr. Swaminathan cited clinical trial data from MD Anderson Cancer Center that showed ibrutinib maintained BTK occupancy even after dose reductions. The data were “very much reassuring” that efficacy is not being compromised when prioritizing safety, and Dr. Swaminathan does not hesitate to reduce the dose for any reasonable cause in his practice, he said. However, he does not start patients on reduced doses, though the ongoing TAILOR study on customizing ibrutinib may provide future guidance.

The doctors also discussed the recent data from the CLL17 trial comparing continuous ibrutinib and fixed-duration venetoclax plus either obinutuzumab or ibrutinib. The trial reaffirmed that time-limited therapies are as good as continuous treatment, and the data may help assuage patients who are concerned they are missing out on treatment efficacy by not receiving continuous therapy, said Dr. Swaminathan.

Lastly, Drs. Swaminathan and Bharti considered secondary lymphoid malignancies in patients with CLL. It is an ongoing question of whether secondary malignancies in CLL, whether non-melanoma skin cancer or solid tumors, are driven by treatments or by the underlying CLL.  Data shown at ASH 2025 did signal a higher risk of secondary malignancies in patients treated with a covalent BTK inhibitor. If further research validates a higher risk of secondary malignancies related to treatment, that may support favoring time-limited regimens to reduce long-term risk, Dr. Swaminathan said.