January 03, 2020
Idelalisib is safe and improves survival rates among patients with relapsed/refractory chronic lymphocytic leukemia (CLL) compared with rituximab monotherapy, according to long-term efficacy and safety results from a phase 3 extension study (J Clin Oncol. 2019 Apr 17. Epub ahead of print).
“A randomized, double-blind, phase III study of idelalisib…plus rituximab versus placebo plus rituximab in patients with relapsed [CLL]… was terminated early because of superior efficacy of the IDELA [idelalisib]-plus-rituximab… arm,” explained Jeff P. Sharman, MD, US Oncology, Willamette Valley Cancer Institute and Research Center, Eugene, Oregon, and colleagues.
“Patients in either arm could then enroll in an extension study to receive IDELA monotherapy,” they added.
The primary study enrolled 220 patients who were randomly assigned in a 1:1 ratio to receive rituximab combined with idelalisib (n = 110) or placebo (n = 110). The primary end points were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety.
A total of 161 patients transitioned to the extension study, including 75 patients from the rituximab plus idelalisib arm and 86 patients from the rituximab plus placebo arm. The long-term efficacy and safety of idelalisib was assessed in the 110 patients who received ≥1 doses of idelalisib in the primary study.
Among patients who transitioned from rituximab plus idelalisib to idelalisib alone, the median PFS was 20.3 months (95% CI, 17.3-26.3 months) after a median follow-up of 18 months. The ORR was 85.5% (95% CI, 77.5%-91.5%), and 1 complete response was reported.
The median OS was 40.6 months among patients who received rituximab plus idelalisib (95% CI, 28.5 to 57.3 months) and 34.6 months (95% CI, 16.0 months to not reached) for patients who received rituximab plus placebo in the primary study.
Increased incidences of all-grade, grade 2, and grade ≥3 diarrhea (46.4%, 17.3%, and 16.4%, respectively); all-grade and grade ≥3 colitis (10.9% and 8.2%, respectively); and all-grade and grade ≥3 pneumonitis (10.0% and 6.4%, respectively) were reported with prolonged exposure to idelalisib. However, the frequency of elevated hepatic aminotransferases did not increase.
“The longer-term data presented here confirm the previously reported efficacy of targeting PI3K with idelalisib in patients with relapsed/refractory CLL and support the use of IDELA/R in this patient population with careful management of potential [adverse events],” Dr Sharman and colleagues concluded.