In an article published in the Journal of Clinical Oncology, Sharman et al provided long-term findings of a phase III trial that examined the addition of idelalisib to rituximab in relapsed chronic lymphocytic leukemia (CLL), including findings from an extension phase of idelalisib monotherapy. The trial was stopped early due to superior efficacy in the idelalisib/rituximab group and supported the 2014 approval of idelalisib in this setting.
In the double-blind trial, 220 patients were randomly assigned to receive rituximab plus idelalisib (n = 110) or rituximab plus placebo (n = 110). After the study was stopped, patients in either group could enroll in an extension study to receive idelalisib monotherapy until disease progression. The long-term efficacy and safety of idelalisib treatment was assessed in 110 patients who received at least 1 dose of idelalisib in the primary study, including 75 who enrolled in the extension study (idelalisib/rituximab–to-idelalisib group). Overall, 86 patients in the initial rituximab group enrolled in the idelalisib monotherapy extension.
In the primary study, the median progression-free survival was 19.4 months in the idelalisib/rituximab group vs 6.5 months in the rituximab group. After a median follow-up of 18 months, the idelalisib/rituximab–to-idelalisib group had median progression-free survival of 20.3 months. The objective response rate in the idelalisib/rituximab–to-idelalisib group was 85.5% (83.6% in primary study), and the median duration of response was 21.4 months (not reached in primary study).
Longer-term follow-up for overall survival in the randomized groups showed a median survival of 40.6 months in the idelalisib/rituximab group vs 34.6 months in the rituximab group, including the patients in each group who received idelalisib in the extension phase (hazard ratio = 0.8, P = .1343). Survival rates were 89.3% vs 68.1% at 12 months and 69.8% vs 51.5% at 24 months.
Prolonged exposure to idelalisib in the idelalisib/rituximab–to-idelalisib group was associated with an increased incidence of any-grade (46.4%), grade 2 (17.3%), and grade ≥ 3 diarrhea (16.4%); any-grade (10.9%) and grade ≥ 3 colitis (8.2%); and any-grade (10.0%) and grade ≥ 3 pneumonitis (6.4%), but no increase in the incidence of hepatic aminotransferase elevations.
The investigators concluded, “[Idelalisib] improved [progression-free survival] and [overall survival] compared with rituximab alone in patients with relapsed CLL. Long-term [idelalisib] was effective and had an expected safety profile. No new [idelalisib]-related adverse events were identified with longer exposure.”
Jeff P. Sharman, MD, of US Oncology, Willamette Valley Cancer Institute and Research Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gilead Sciences. For full disclosures of the study authors, visit jco.ascopubs.org.
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