Ibrutinib, a first-in-class, once-daily Bruton’s tyrosine kinase inhibitor, is FDA approved for all patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Prior phase 3 RESONATE study data established the superiority of ibrutinib to ofatumumab in patients with relapsed/refractory CLL or SLL, as measured by progression-free survival (PFS), overall survival (OS), and response (Byrd. NEJM. 2014). Researchers reported updated safety and efficacy results from the RESONATE trial, with up to 4 years’ follow-up.
In the study, patients received ibrutinib 420 mg orally until disease progression, or ofatumumab for up to 24 weeks. At median 9-month follow-up, the Data Monitoring Committee declared the superiority of ibrutinib versus ofatumumab for PFS and OS, and ibrutinib access was recommended for all patients receiving ofatumumab.
A total of 391 patients were randomized to receive ibrutinib (n = 195) or ofatumumab (n = 196). Patients’ median age was 67 years; 57% had Rai stage III/IV disease. After median follow-up of 44 months, PFS was significantly longer for ibrutinib versus ofatumumab (P <0.0001); median PFS was not reached for ibrutinib versus 8 months for ofatumumab. Furthermore, 59% of patients receiving ibrutinib achieved 3-year PFS compared with 3% of patients receiving ofatumumab. A favorable trend in PFS was also seen with ibrutinib for the del11q subgroup; however, outcomes did not achieve significance for other genetic abnormalities. Approximately two-thirds of patients in the ofatumumab arm crossed over to ibrutinib after losing response. OS was longer for ibrutinib versus ofatumumab; median OS was not reached for either arm. The OS at 3 years for patients receiving ibrutinib was nearly three-quarters (74%). Treatment-related toxicities were generally well-tolerated by patients receiving ibrutinib, and adverse event rates were consistent with earlier data. The incidence of most grade 3 or grade 4 adverse events decreased from year 1 to years 2 and 3. Discontinuation was most frequently due to disease progression (27%) and adverse events (12%).
Long-term treatment with ibrutinib in the international phase 3 RESONATE study was well-tolerated and continues to show sustained PFS and OS regardless of high-risk cytogenetics. These data add to the body of evidence supporting ibrutinib as a cornerstone therapeutic option in patients with CLL.
Byrd JC, et al. ASCO Abstract 7510.