Patients With CLL Who Discontinue Alternate Kinase Inhibitor Treatment May Respond to Other Therapies

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).

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.

Reference

1. 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.