In CLL, Imbruvica is indicated for the treatment of adults who have received at least one prior therapy, or as a first line therapy in the presence of 17p depletion or TP53 mutation in patients unsuitable for chemo-immunotherapy.
A higher dose of ibrutinib is recommended in MCL than in CLL (560mg [four capsules] versus 420mg [three capsules] once daily). In both cases treatment should be continued until disease progression or ibrutinib is no longer tolerated.
Ibrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK), the first drug in this class, and has been shown in preclinical studies to effectively inhibit malignant B-cell proliferation and survival in vivo.
Approval of ibrutinib for MCL was based on the results of a single-arm open-label phase II study involving 111 patients with relapsed or refractory MCL treated with ibrutinib 560mg daily until disease progression or unacceptable toxicity. Treatment was associated with an overall response rate of 67.6% (95% CI 58.0-76.1) and a complete response rate of 20.7%, with a median time to initial response of 1.9 months (range 1.4-13.7).
Licensing for the CLL indication was based on the results of an open-label uncontrolled study (n=51) and a randomised controlled open-label phase III study (n=391).
In the uncontrolled study, treatment with ibrutinib 420mg once daily until disease progression or unacceptable toxicity was associated with an overall response rate of 64.7% (95% CI 50.1-77.6%) at a median duration of follow up of 16.4 months, with a median response time of 1.9 months.
In the controlled study, which compared ibrutinib 420mg once daily with ofatumumab 300mg for up to 12 doses, there was a 78.5% (95% CI 68.3-85.4) statistically significant reduction in the risk of death or progression for patients in the ibrutinib group and a 56.6% (95% CI 21.1-76.2) statistically significant reduction in the risk of death.
The most commonly reported adverse reactions in studies were gastrointestinal upset, musculoskeletal pain, upper respiratory tract infection, bruising, rash, fever and neutropenia.
Further information: Janssen-Cilag