Most patients with chronic lymphocytic leukemia (CLL) who discontinue treatment with B cell receptor signal transduction kinase inhibitors (KI) respond to alternate KI therapy, a study has found.1
The multicenter retrospective analysis included 123 patients with CLL who had discontinued treatment with ibrutinib (93 patients) or idelalisib (30 patients). The study’s primary endpoint was post KI progression-free survival (PFS) as determined by the Kaplan Meier method.
Results found that 10% of patients who received ibrutinib and 32% of patients who received idelalisib were initiated at doses lower than the U.S. Food and Drug Administration labeled doses.
Doses were modified or held in 23% and 42% of ibrutinib patients and 30% or 65% of idelalisib patients prior to discontinuation. Discontinuation was mostly attributed to toxicities (58% ibrutinib; 60% idelalisib), CLL progression (24% vs 30%, respectively), and RT diffuse large B cell lymphoma (8% vs 7%, respectively.
At a median follow-up of 6 months, median PFS was 9 months after treatment initiation, and those with RT had a significantly inferior rate (5 months RT vs 8 months progression vs 9 months toxicity; P = .04).
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Overall response rate for patients who received non-KI therapies following discontinuation with KI therapies was 40%. Response to alternate KI treatment was similar in those who had discontinued due to toxicity (ORR 60% PR + PRL) and progression (ORR 67% PR + PRL). PFS at a median follow-up of 5 months was not reached in patients had been treated with an alternate KI therapy vs 7 months with non-KI therapies.
- Mato A, Nabhan C, Barr PM et al. Favorable outcomes in CLL pts with alternate kinase inhibitors following ibrutinib or idelalisib discontinuation: results from a large multi-center study [abstract]. Blood. 2015;126(23):719.