Health Canada recently approved the Bruton tyrosine kinase inhibitor ibrutinib (Imbruvica) for the treatment of chronic lymphocytic leukemia (CLL).
The drug can now be used to treat CLL patients, including those with 17p deletion, who have received at least one prior therapy. It can also be used as frontline treatment in CLL patients with 17p deletion.
Health Canada’s approval of ibrutinib is based on results of the phase 3 RESONATE trial, which were presented at this year’s ASCO and EHA meetings.
The trial included 391 previously treated patients, 127 of whom had 17p deletion. Patients were randomized to receive ibrutinib or the anti-CD20 monoclonal antibody ofatumumab until disease progression or unacceptable toxicity.
The trial was stopped early after a pre-planned interim analysis showed that ibrutinib-treated patients experienced a 78% reduction in the risk of disease progression or death.
At the time of interim analysis, the patients’ median time on study was 9.4 months. The best overall response among evaluable patients was 78% in the ibrutinib arm and 11% in the ofatumumab arm.
Ibrutinib significantly prolonged progression-free and overall survival. The median progression-free survival was 8.1 months in the ofatumumab arm and was not reached in the ibrutinib arm (P<0.0001). The median overall survival was not reached in either arm, but the hazard ratio was 0.434 (P=0.0049).
Of the 127 patients with 17p deletion, those treated with ibrutinib experienced a 75% reduction in the risk of disease progression or death.
Adverse events occurred in 99% of patients in the ibrutinib arm and 98% of those in the ofatumumab arm. Grade 3/4 events occurred in 51% and 39%, respectively.
Atrial fibrillation, bleeding-related events, diarrhea, and arthralgia were more common in the ibrutinib arm. Infusion-related reactions, peripheral sensory neuropathy, urticaria, night sweats, and pruritus were more common in the ofatumumab arm.
Ibrutinib is being developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics, Inc. Janssen will commercialize the drug in Canada, and Janssen affiliates will commercialize it around the world, except in the US, where Pharmacyclics and Janssen Biotech, Inc. co-market it.
