A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib and Rituximab for Previously Treated Patients with Chronic Lymphocytic Leukemia
Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues. Furman and colleagues conducted a phase 3 trial that evaluated and compared the efficacy and safety of idelalisib plus rituximab (IDELA + R) and placebo plus rituximab (placebo + R). The study’s primary end point was progression-free survival (PFS). Response and progression were assessed by an independent review committee using standard criteria.
A total of 220 patients enrolled in this trial. All patients had previously treated CLL that warranted therapy, but were unfit to receive cytotoxic agents because of comorbidities, renal dysfunction, or cytopenias due to poor bone marrow reserve. The patients’ median age was 72 years. Based on a prespecified interim analysis, Furman and colleagues reported that the PFS in the IDELA + R arm was significantly superior to the PFS in the placebo + R arm (hazard ratio [HR], 0.15). The median PFS of patients treated with IDELA + R was not reached and the median PFS of patients treated with placebo + R was 5.5 months. At 24 weeks, the PFS was 93% in the IDELA + R arm compared with 46% in the placebo + R arm. PFS strongly favored IDELA + R in all patient subgroups, including those with high-risk features.
Patients treated with IDELA + R also had a superior overall response rate (ORR) relative to patients in the placebo + R arm (81% vs 13%) and a higher lymph node response rate (93% vs 4%). Compared with patients in the placebo +R arm, patients treated with IDELA + R also had a significant improvement in the overall survival (HR, 0.28; P=.018).
The most common adverse events (AEs) in patients treated with IDELA + R were pyrexia, fatigue, nausea, chills, diarrhea, infusion-related reactions, and cough; select laboratory abnormalities included alanine aminotransferase elevation, anemia, neutropenia, and thrombocytopenia. The most common serious AEs in patients treated with IDELA + R were pneumonia, pyrexia, and febrile neutropenia. Overall, 8% of patients treated with IDELA + R and 10% of patients treated with placebo + R discontinued the treatment drug because of AEs.
Furman and colleaguesconcluded that, in heavily pretreated unfit patients with relapsed CLL, including those with unfavorable genetic features, treatment with IDELA + R resulted in significant improvements in efficacy outcomes with an acceptable safety profile, compared with findings from the placebo + R arm.
Furman RR, Sharman JP, Coutre SE, et al. A phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib and rituximab for previously treated patients with chronic lymphocytic leukemia (CLL). Blood. 2013;122(21). Late-Breaking Abstract 6.