Final results from the phase 3 RESONATE trial (ClinicalTrials.gov Identifier: NCT01578707) suggest that ibrutinib may be more effective than ofatumumab for treating patients with relapsed or refractory chronic lymphocytic leukemia (CLL). The results were published in the American Journal of Hematology.
Earlier results from RESONATE suggested that single-agent ibrutinib, a Bruton’s tyrosine kinase inhibitor administered once daily, has greater efficacy compared with ofatumumab for treating patients with CLL/small lymphocytic lymphoma, including those with high-risk features such as 17p deletion, TP53 mutation, 11q deletion, or unmutated IGHV. For this analysis, the authors reviewed long-term safety and efficacy data.
A total of 195 patients were randomly assigned to receive ibrutinib and 196 received ofatumumab. The median duration of treatment was 41 months (range, 0.2-71.1) with ibrutinib and 5.3 months (range, 0-9.0) with ofatumumab; the planned duration with the latter, however, was 24 weeks. Of the 196 patients receiving ofatumumab, 68% (133) crossed over to the ibrutinib treatment arm.
Median overall follow-up was 74 months. Median progression-free survival (PFS) was 44.1 months with ibrutinib and 8.1 months with ofatumumab (hazard ratio [HR], 0.148; P <.001). PFS was also better in the high-risk patient group that received ibrutinib compared with high-risk patients who received ofatumumab (HR, 0.110).
Overall survival was better in the ibrutinib group (67.7 vs 65.1 months), even after adjusting for crossover (HR, 0.639).
Frequently reported grade 3 or worse adverse events in the ibrutinib group included neutropenia (25%), pneumonia (21%), thrombocytopenia (10%), anemia (9%), hypertension (9%), urinary tract infection (7%), diarrhea (7%), and atrial fibrillation (6%). The prevalence of grade 3 or worse adverse events in patients receiving ibrutinib was 62% in the first year of treatment and decreased to 32% by the sixth year of treatment.
At study termination, 36.9% of patients who received ibrutinib discontinued treatment due to progressive disease, 16.4% due to adverse events, 7.7% due to withdrawal from study, 6.7% due to death, 10.3% due to investigator decision, and 22.1% due to study termination by sponsor. Of the 133 patients who crossed over from the ofatumumab group, 47 were still receiving therapy at study closure.
“These 6-year follow-up results from the RESONATE study confirm the robust and durable efficacy of ibrutinib with extended treatment in patients with relapsed or refractory CLL,” the researchers wrote.
1. Munir T, Brown JR, O’Brien S, et al. Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma [published online September 11, 2019]. Am J Hematol. doi:10.1002/ajh.25638