The use of ibrutinib appeared superior to idelalisib in all settings as a first-choice kinase inhibitor for the treatment of chronic lymphocytic leukemia, according to study results presented at the ASH Annual Meeting and Exposition.
The study results also demonstrated that venetoclax appeared superior to chemoimmunotherapy combinations in the setting of first-choice kinase inhibitor failure.
Anthony R. Mato, MD, MSCE, director of the Center for Chronic Lymphocytic Leukemia at the Hospital of the University of Pennsylvania, and colleagues conducted a multicenter, retrospective analysis of 683 patients with CLL treated with either ibrutinib (Imbruvica; Janssen, Pharmacyclics), idelalisib (Zydelig, Gilead) or venetoclax (Venclexta; AbbVie, Genentech) to assess optimal sequencing and patterns of treatment failure.
Overall response rate in patients who received ibrutinib (n = 621) as their first kinase inhibitor was 69% and ORR in patients who received idelalisib (n = 62) was 81%.
Median PFS and OS for the entire cohort was 35 months. Patients treated with ibrutinib had significantly better PFS in front-line (HR = 2.8; 95% CI, 1.9-4.1), clinical trials (HR = 3.3; 95% CI, 1.8-5.9), commercial use (HR = 2.5; 95% CI, 1.5-4) and complex karyotype (HR = 2.5; 95% CI, 1.2-5.2) settings.
At the time of treatment failure, the use of either an alternative kinase inhibitor or venetoclax (n = 65) was associated with superior PFS when compared with chemoimmunotherapy combinations (P = .001).
Additionally, patients who failed ibrutinib had a minimally better PFS when treated with venetoclax versus idelalisib (HR = 0.6; 95% CI, 0.3-1).
“These data provide guidance for sequencing of novel agents and support the need for trials directly comparing novel agents and sequencing strategies in CLL,” Mato and colleagues wrote. – by Ryan McDonald
Reference: Mato AR, et al. Poster 4400. Presented at: The ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: Mato reports serving as a consultant for Abbvie, Gilead Sciences, Pharmacyclics and TG Therapeutics.