Extended Ibrutinib Treatment in RESONATE CLL Trial
Posted: Wednesday, September 11, 2019
Up to 6 years of follow-up data from the RESONATE trial indicate that in patients with previously treated relapsed or refractory chronic lymphocytic leukemia (CLL), extended ibrutinib treatment yielded “sustained efficacy.” These results, which were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 7510) by Jennifer R. Brown, MD, of Dana-Farber Cancer Institute, Boston, and colleagues from various institutions, also showed efficacy in patients with high-risk genomic features.
“Safety remained acceptable, with low rates of [discontinuation] due to [adverse events], and with no new safety signals over long-term therapy,” the authors concluded. “These results establish long-term benefit and tolerability for continuous [ibrutinib] treatment in [patients] with [relapsed or refractory] CLL.”
In this phase III study (ClinicalTrials.gov identifier NCT01578707), 391 patients were randomly assigned to ibrutinib (420 mg daily) or intravenous ofatumumab for up to 24 weeks. Of the 195 patients in the ibrutinib cohort, 86% were categorized in the genomic high-risk population, with 79% of the 196 patients treated with ofatumumab classified as high risk.
The investigators observed significant sustained progression-free survival for patients treated with ibrutinib versus ofatumumab (44.1 vs. 8.1 months, respectively). Among the genomic high-risk population, patients treated with ibrutinib had a progression-free survival of 44.1 months versus 8.0 months in the ofatumumab cohort (hazard ratio = 0.11). The objective response rate was 88% in the ibrutinib group, and initial ibrutinib treatment conferred better overall survival than ofatumumab when censored for crossover (hazard ratio = 0.64).
During long-term ibrutinib therapy, all-grade hypertension and arterial fibrillation occurred in 21% and 12% of patients, respectively, with major hemorrhage in 10% of the population. The most common reasons for ibrutinib discontinuation prior to study completion were progressive disease (37%) and adverse events (16%).
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.