By Patrick Daly - Last Updated: March 19, 2024
Treatment with ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) followed by two years of ibrutinib maintenance induced durable and deep responses in patients with chronic lymphocytic leukemia (CLL) with diverse genetic markers, according to a study published in Blood Advances.
“Given the long time horizon for younger patients with CLL in terms of life expectancy, the significant expense associated with continuous [Bruton’s tyrosine kinase (BTK)] inhibition, and the logistical challenges of initiation with time-limited venetoclax-based combinations, time-limited combinations of a BTK inhibitor plus FCR represent a promising treatment strategy for this select group of patients with CLL and should be explored further in larger comparative studies,” wrote the authors, led by Inhye Ahn, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts
The report was based on updated data from a phase II study after a median follow-up of 63 months. Among 85 patients initially enrolled in the trial, 91% completed iFCR and two years of ibrutinib maintenance. Five-year progression-free survival (PFS) was 94% (95% CI, 89-100) and five-year overall survival was 99% (95% CI, 96-100). The authors reported no differences in PFS according to immunoglobulin heavy-chain variable region gene status or duration of ibrutinib maintenance.
A total of 13 patients developed measurable residual disease (MRD) conversion without disease progression, 77% of which occurred after stopping ibrutinib. No conversions had BTK mutations, while one had PLCG2 mutation. Six of the 13 patients underwent ibrutinib retreatment with a median duration on retreatment of 34 months.
The cumulative incidence of atrial fibrillation in the cohort was 8%, and second malignancy or nonmalignant hematologic disease occurred in 13%—mostly nonmelanoma skin cancer.
“Overall, iFCR with two-year [ibrutinib maintenance] achieved durably deep responses in patients with diverse CLL genetic markers. Re-emergent clones lacked BTK mutation and retained sensitivity to ibrutinib upon retreatment,” Dr. Ahn and colleagues concluded.
Reference
Ahn IE, Brander DM, Ren Y, et al. Five-year follow-up of a phase 2 study of ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial therapy in CLL. Blood Adv. 2024;8(4):832-841. doi:10.1182/bloodadvances.2023011574
Original Source: Ibrutinib-based Therapy Provides Promising Responses in CLL | Blood Cancers Today