Despite significant toxicities, idelalisib improved time to progression for patients with treatment-resistant chronic lymphocytic leukemia (CLL), according to interim findings from a phase III randomized, placebo-controlled study published in The Lancet Oncology.
At a median follow-up of 14 months, median progression-free survival was 20.8 months among 207 patients administered idelalisib versus 11.1 months in the study’s 209 placebo-arm patients, authors reported (hazard ratio [HR], 0.33; 95% CI 0.25–0.44; P < .0001).
“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,” reported Professor Andrew D. Zelenetz, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in New York.
“However, careful attention needs to be paid to management of serious adverse events and infections associated with this regimen during treatment selection,” he cautioned.
Study participants received bendamustine plus rituximab for up to 6 cycles, and either twice-daily idelalisib or placebo until their disease progressed or toxicities became intolerable.
The most frequent grade 3+ toxicities among patients receiving idelalisib included neutropenia (60% vs 47% in the placebo arm) and febrile neutropenia (23%). Serious adverse events (febrile neutropenia, pneumonia, and fever) occurred in 68% of patients administered idelalisib, compared to 44% in the placebo group.
The adverse event-related treatment discontinuation rate for patients administered idelalisib was twice as high as that seen in the placebo group (27% vs 13%). Eleven percent of patients in the idelalisib group died of treatment-emergent adverse events, compared to 7% in the placebo group.
The increased rate of infections among patients administered idelalisib was similar to those noted in previous reports for idelalisib combined with bendamustine and rituximab in first-line CLL settings and for relapsed indolent non-Hodgkin lymphoma, noted Francesca R. Mauro, MD, PhD, of Sapienza University in Rome, Italy, in a companion commentary published alongside the study. Cytomegalovirus infection monitoring, prophylactic therapy against opportunistic Pneumocystis jirovecii infection, and repeated granulocyte-count blood tests should reduce infection rates for patients taking idelalisib, Mauro wrote.