Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) had significant delays in progression and death when treated with the first-in-class PI3k delta inhibitor idelalisib in combination with bendamustine and rituximab compared with bendamustine/rituximab alone, according to the results of a phase III trial (abstract LBA-5) presented at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition.
The phase III study was unblinded after an interim analysis showed an “overwhelming benefit” in favor of the study drug, according to Andrew D. Zelenetz, MD, PhD, of the Memorial Sloan Kettering Cancer Center in New York, who presented results of the study at a press conference.
“There was a 67% reduction in risk for progression or death and there was a 45% reduction in risk of death from relapsed/refractory CLL,” said Zelenetz.
The study included 416 patients with relapsed/refractory CLL enrolled between June 2012 and August 2014. All patients had to have prior treatment with a therapy containing purine analog or bendamustine, prior treatment with an anti-CD20 antibody, progression of disease within 36 months of the completion of their last prior therapy, and be fit enough to receive cytotoxic chemotherapy.
Patients were randomly assigned to 6 cycles of bendamustine/rituximab every 28 days plus idelalisib 150 mg twice daily or bendamustine/rituximab plus placebo, and continued on treatment until progression, death, intolerable toxicity, or trial withdrawal. The interim analysis took place when 67% of planned events of CLL progression or death occurred.
The median progression-free survival was 23.1 months for idelalisib plus bendamustine/rituximab compared with 11.1 months for bendamustine/rituximab alone (hazard ratio [HR], 0.33; P < .0001). According to Zelenetz the progression-free survival benefit was consistent across all examined subgroups.
“The 11.1 months in relapsed/refractory CLL is very consistent with what we would expect for bendamustine and rituximab so this represents a substantial increase in the progression-free survival,” Zelenetz said.
The addition of idelalisib resulted in a significant improvement in overall survival compared with bendamustine/rituximab alone (HR, 0.55; P = .008). The median overall survival was not reach for either study arm.
Almost all patients enrolled in the trial experience toxicity. Serious adverse events were more common among patients assigned the study drug compared with placebo (93% vs 76%). In addition, more patients assigned idelalisib had study drug discontinuation compared with the control arm (26% vs 13%).
Based on these results, Zelenetz concluded that “idelalisib plus bendamustine/rituximab represents an important new option over a standard of care bendamustine/rituximab.”