Adding Idelalisib to Bendamustine and Rituximab Improves PFS in CLL

Adding idelalisib to bendamustine plus rituximab significantly prolonged progression-free survival (PFS) compared with chemoimmunotherapy alone among patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to a study published in The Lancet Oncology.¹

Novel therapies are needed to improve outcomes for patients in this setting. Researchers evaluated the efficacy and safety of adding idelalisib, a phosphoinositide-3-kinase δ inhibitor approved in combination with rituximab for relapsed CLL, to bendamustine plus rituximab.

For the international, double-blind, phase 3 trial (ClinicalTrials.gov Identifier: NCT01569295), investigators enrolled 416 adult patients with relapsed or refractory CLL who had measurable lymphadenopathy and had experienced disease progression within 36 months since last prior therapy.

Participants were randomly assigned 1:1 to receive a maximum of 6 cycles of bendamustine plus rituximab with either oral idelalisib or placebo given twice daily until disease progression or unacceptable toxicity.

Median follow-up was 14 months. Treatment with idelalisib significantly reduced the risk of progression or death by 67% compared with bendamustine plus rituximab alone (hazard ratio, 0.33; 95% CI, 0.25-0.44; P < .0001). Median progression-free survival was 20.8 months (95% CI, 16.6-26.4) in the idelalisib arm vs 11.1 months (95% CI, 8.9-11.1) in the placebo arm.

The most common grade 3 or worse adverse events among idelalisib-treated patients were neutropenia (60%) and febrile neutropenia (23%). The most frequent grade 3 or worse adverse events in the placebo group were neutropenia (47%) and thrombocytopenia (13%). Investigators also observed an increased risk of infection in the idelalisib arm.

Eleven percent of patients in the experimental group died due to treatment-emergent adverse events compared with 7% in the control arm.

The authors concluded that the findings demonstrate a significant improvement in progression-free survival with idelalisib in this population. Clinicians prescribing this drug combination should, however, carefully monitor for serious adverse events and infections associated with this regimen.

Reference

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]