Ibrutinib also significantly prolonged OS compared with ofatumumab (HR, 0.434; 95% CI: 0.238-0.789, log-rank P = 0.0049); this 57% reduction in risk of death for the ibrutinib arm included 57 patients who crossed over to ibrutinib following disease progression on ofatumumab.
Overall response to therapy by IRC assessment was 63% in the ibrutinib arm, which included 20% partial responses (PRs) with lymphocytosis and 43% PRs, compared with 4% in the ofatumumab arm, all PRs. A total of 32% of patients in the ibrutinib arm had stable disease (SD) compared with 78% in the ofatumumab arm.
By investigator assessment, response was 85% in the ibrutinib arm, which included 2% complete responses, 15% PRs with lymphocytosis, and 68% PRs; 11% had SD. In comparison, ORR was 23% in the ofatumumab arm, which included 1% CRs, 2% PRs plus lymphocytosis, and 21% PRs; 54% had SD.
Best IRC response without a second CT confirmation in the intent-to-treat population was 75% for ibrutinib versus 11% for ofatumumab and, in the evaluable population, 78% versus 12%. In the ibrutinib arm, 50% reduction in lymph nodes was 92% versus 17% in the ofatumumab arm.
Atrial fibrillation of any grade was noted more frequently in the ibrutinib arm (n = 10)—which led to treatment discontinuation in one patient—than in the ofatumumab arm (n = 1). Dr. Byrd said bleeding-related adverse events of any grade were more common with ibrutinib than with ofatumumab, 44% versus 12%; these were primarily petechiae and included ecchymoses.
The Food and Drug Administration approved ibrutinib for the treatment of CLL in February 2014.
The RESONATE study results were published online in the New England Journal of Medicine on May 31.
- Byrd JC, Brown JR, O’Brien SM et al. Abstract LBA7008. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.