CHICAGO, IL—Ibrutinib significantly improved progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) when compared with ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the phase 3 RESONATE study concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
“This study validates ibrutinib as an effective new single-agent therapy” for these patients, said John C. Byrd, MD, a Professor of Medicine at The Ohio State University Comprehensive Cancer Center in Columbus, OH.
The RESONATE study found that the effect of ibrutinib on PFS was observed regardless of baseline clinical characteristics or molecular features, including the high-risk del17p and purine-refractory subgroups.
Between June 2012 and April 2013, investigators randomly assigned patients with disease progression after two or more prior therapies to oral ibrutinib 420 mg once daily (n = 195) or intravenous ofatumumab at an initial dose of 300 mg followed by 2,000 mg for 11 doses over 24 weeks (n = 196). A total of 57 patients on the ofatumumab arm were allowed to crossover to ibrutinib 420 mg once daily after progressive disease was confirmed by the independent review committee (IRC) in August 2013.
The primary study objective was PFS, as assed by IRC per International Workshop on CLL criteria with the 2012 clarification for treatment-related lymphocytosis. Secondary objectives were OS, IRC-assessed ORR, safety, and tolerability. An exploratory objective was investigator-assessed ORR.
Baseline characteristics were well balanced; median age was 67 years in both arms, and 40% of the patients were older than 70 years. In the ibrutinib and ofatumumab ams, respectively, 66% and 70% of patients were male, and 32% and 33% had the del17p; 45% of patients in both arms were refractory to purine analogs.
Ibrutinib reduced risk of progression by 78%, Dr. Byrd said, with median PFS not reached compared with 8.1 months for ofatumumab (hazard ratio [HR], 0.215; 95% CI: 0.146-0.317, P < 0.0001). The investigator-assessed PFS HR was 0.133 (95% CI: 0.085-0.209, P < 0.0001). When PFS was assessed by baseline characteristics and molecular features, the HRs all favored ibrutinib.