Data from the phase III RESONATE trial showed that monotherapy ibrutinib significantly lengthened progression-free survival and overall survival compared to ofatumumab in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic leukemia.
The trial results were presented at the annual meeting of the American Society of Clinical Oncology June 3 and were simultaneously published in The New England Journal of Medicine.
The median PFS in the ibrutinib arm was not reached because progression events occurred more slowly than in the ofatumumab arm. The PFS results represent a 79 percent reduction in the risk of progression or death in patients treated with ibrutinib compared to ofatumumab. PFS in the ofatumumab arm was 8.1 months (HR 0.215, 95% CI, 0.146 to 0.317; P<0.0001).
The OS median was also not reached in either arm because progression events occurred slowly. The OS results represent a 57 percent reduction in the risk of death in patients receiving ibrutinib versus those in the ofatumumab arm. The median follow-up was 9.4 months.
Additionally, the ORR was significantly higher in patients taking ibrutinib monotherapy versus ofatumumab monotherapy, regardless of response criteria or baseline characteristics. Overall, 43 percent of ibrutinib patients achieved a partial response (PR) compared to only four percent of patients taking ofatumumab (p<0.0001), following the International Workshop on CLL (IWCLL) response criteria requiring response to be confirmed for at least two months.
An additional 20 percent of ibrutinib treated patients also achieved a PR with lymphocytosis. Investigator-assessed response rates were 85 percent for ibrutinib and 24 percent for patients receiving ofatumumab. Significantly higher response rates were seen in the ibrutinib arm consistently across all baseline sub-groups, including those with a deletion of the short arm of chromosome 17, a genetic mutation typically associated with poor prognoses, or refractory to a purine analogue.
RESONATE is an international, open-label, randomized study that examined ibrutinib monotherapy versus ofatumumab monotherapy in relapsed or refractory patients with CLL/SLL who had received at least one prior therapy and were not considered appropriate candidates for treatment with a purine analog (n=391). Patients were administered either 420 mg oral ibrutinib (n=195) once-daily until progression or unacceptable toxicity or intravenous ofatumumab for up to 24 weeks (n=196, initial dose of 300 mg followed by 11 doses at 2,000 mg, per dose and schedule consistent with local labeling).
Ibrutinib is a Bruton’s tyrosine kinase inhibitor, and is marketed as Imbruvica in the U.S., where it received FDA approval for the treatment of patients with MCL who have received at least one prior therapy and for the treatment of patients with CLL who have received at least one prior therapy.
In 2011, Janssen and Pharmacyclics Inc. entered into an agreement to jointly develop and commercialize ibrutinib.
