Credit: Rhoda Baer
The US Food and Drug Administration (FDA) has expanded the indication for the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica).
Last November, the drug gained accelerated approval as a “breakthrough therapy” for patients with mantle cell lymphoma who had received at least 1 prior therapy.
Now, ibrutinib has been granted accelerated approval to treat patients with chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy.
The accelerated approval process allows the FDA to approve a drug based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Both approvals of ibrutinib are based on observed benefits in overall response rates.
Ibrutinib also received priority review and orphan-product designation for CLL.
Trial results
The accelerated approval of ibrutinib is based on results of a phase 1b/2 study, which included 48 patients with relapsed or refractory CLL. The patients had been diagnosed an average of 6.7 years prior to study enrollment and had received 4 prior therapies.
All patients received 420 mg of ibrutinib orally until disease progression or the development of unacceptable toxicity.
The overall response rate was 58.3%, and all of these were partial responses. The median duration of response was not reached (range, 5.6 months to more than 24.2 months).
Study investigators have not established whether ibrutinib confers improvements in survival or disease-related symptoms.
The median treatment duration was 15.6 months. Ten percent of patients (n=5) discontinued treatment due to adverse events. Three of these patients developed infections, and 2 had subdural hematomas. Thirteen percent of patients experienced adverse events that led to dose reductions.
The most commonly occurring adverse events (all grades and grade 3/4, respectively) included thrombocytopenia (71%, 10%), diarrhea (63%, 4%), bruising (54%, 2%), neutropenia (54%, 27%), anemia (44%, 0%), upper respiratory tract infection (48%, 26%), fatigue (31%, 4%), musculoskeletal pain (27%, 6%), rash (27%, 0%), pyrexia (25%, 2%), constipation (23%, 2%), peripheral edema (23%, 0%), arthralgia (23%, 0%), nausea (21%, 2%), stomatitis (21%, 0%), sinusitis (21%, 6%), and dizziness (21%, 0%).
Ibrutinib is being developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. For full prescribing information, visit http://www.imbruvica.com/downloads/Prescribing_Information.pdf.
