The addition of idelalisib to bendamustine plus rituximab significantly increased progression-free survival (PFS) compared to bendamustine plus rituximab alone in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).1
PI3K inhibitors are a class of drugs that work by blocking 1 or more PI3K enzymes. These drugs suppress tumor growth by blocking PI3K enzymes.
This double-blind, placebo-controlled, international study assessed the safety and efficacy of adding idelalisib to bendamustine plus rituximab in adult patients (18 years and older).
All patients had relapsed or refractory CLL requiring treatment and had measurable lymphadenopathy by CT or MRI. Enrolled patients experienced disease progression within 36 months since their last previous treatment.
Between June 2012 and August 2014, Patients (N = 416) were randomly assigned (1:1) to the idelalisib with bendamustine plus rituximab (n = 207) and placebo with bendamustine plus rituximab (n = 209) groups. High-risk features (IGHV, del[17p], or TP53 mutation) and refractory vs relapsed disease stratified randomization.Patients received treatment until disease progression or intolerable study drug-related toxicity.
Median progression-free survival for patients receiving idelalisib was 20.8 months (95% CI, 16.6-26.4) and for patients receiving placebo, 11.1 months (95% CI, 8.9-11.1; hazard ratio [HR] 0.33; 95% CI, 0.25-0.44; P <.0001). Median follow-up was 14 months.
The most frequent grade 3 or worse adverse events (AEs) in the treatment group were neutropenia (60%) and febrile neutropenia (23%). The most frequent grade 3 or worse AEs in the placebo group were neutropenia (47%) and thrombocytopenia (13%).
The idelalisib group also experienced an increased risk of infection compared with the placebo group (grade 3 or higher infections and infestations: 80 of 207 [39%] vs 52 of 209 [25%]).
Serious adverse effects were more common in the idelalisib group than the placebo group (68% vs 44%). These included febrile neutropenia, pneumonia, and pyrexia.
Treatment-emergent AEs resulting in death occurred in 23 (11%) patients in the idelalisib group and 15 (7%) patients in the placebo group. Six deaths due to infection occurred in the idelalisib group, and 3 deaths due to infection occurred in the placebo group.
“Idelalisib in combination with bendamustine plus rituximab improved progression-free survival compared with bendamustine plus rituximab alone in patients with relapsed or refractory chronic lymphocytic leukemia,” concluded the investigators.
“However, careful attention needs to be paid to management of serious adverse events and infections associated with this regimen during treatment selection.”
This trial is ongoing and funded by Gilead Sciences Inc.
1. Zelenetz AD, Barrientos JC, Brown JR, et al. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017 Jan 27. doi: 10.1016/S1470-2045(16)30671-4 [Epub ahead of print]