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.
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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.
- 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]