Idelalisib combined with rituximab improved outcomes compared with rituximab alone in patients with relapsed and refractory chronic lymphocytic leukemia (CLL) in a long-term study of efficacy and safety, according to the final report published in the Journal of Clinical Oncology.
The report included long-term efficacy and safety data for idelalisib-treated patients across a primary study (ClinicalTrials.gov Identifier: NCT01539512), which was terminated early in August 2013 due to the superior efficacy of idelalisib plus rituximab over the placebo, and an extension study (ClinicalTrials.gov Identifier: NCT01539291). The primary study was a randomized, 2-arm, double blind, placebo-controlled, phase 3 study; after it was terminated, the extension study was unblinded. Patients who transitioned to the extension study received idelalisib monotherapy (150 mg twice daily). The key endpoints were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety.
From the primary study, 161 patients transitioned to the extension study: 75 patients from the idelalisib plus rituximab arm and 86 patients from the placebo and rituximab arm. Median follow-up time was 18 months (range, 0.3-67.6). Median PFS and ORR of the idelalisib plus rituximab to idelalisib group were 20.3 months (95% CI: 17.3-26.3) and 85.5% (94/110), respectively. Median OS was 40.6 months (95% CI: 28.5-57.3) for patients in the idelalisib plus rituximab and 34.6 months (95% CI: 16.0- not reached) for patients in the placebo plus rituximab group.
Median duration of exposure to idelalisib was 8.1 months in the primary study and 16.2 months across the primary and extension studies. In the primary study, the most frequently reported adverse events in the idelalisib plus rituximab group were pyrexia (40.0%), fatigue (30.9%), and diarrhea (29.1%, with 17.3% experiencing grade 2 or greater). With longer exposure to idelalisib, the occurrence of diarrhea increased (46.4%; 33.6% experienced grade 2 or greater). The incidence of all grades of colitis and pneumonitis also increased with longer idelalisib exposure.
The authors concluded that this longer term study “confirmed the previously reported efficacy of targeting PI3K with idelalisib in patients with relapsed/refractory CLL and support the use of idelalisib plus rituximab in this patient population with careful management of potential adverse events.”
1. Sharman JP, Coutre SE, Furman RR, et al. Final results of a randomized, phase III study of rituximab with or without idelalisib followed by open-label idelalisib in patients with relapsed chronic lymphocytic leukemia [published online April 17, 2019]. J Clin Oncol. doi:10.1200/JCO.18.01460