On January 12, 2014, the FDA approved a new indication for ibrutinib (Imbruvica; Pharmacyclics) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least 1 previous therapy, using the agency’s accelerated approval process.
The drug also received an orphan drug designation from the FDA.
The approval of ibrutinib for CLL is based on the results from a clinical trial with 48 patients who had received 4 previous therapies. Patients received oral ibrutinib until disease progression or until unacceptable toxicity. Overall response was nearly 58%, with a response duration of 5.6 months to 24.2 months during the study. No improvement in survival or disease-related symptoms has been established.
The most common side effects reported with ibrutinib include thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, pyrexia, constipation, peripheral edema, arthralgia, nausea, mouth sores, sinusitis, and dizziness.
Expanded indication. On July 28, 2014, the FDA expanded the indication of ibrutinib for patients with CLL who have a deletion in chromosome 17 (17p deletion), which leads to poor response to standard CLL therapies. With this new indication, the FDA also approved a new labeling for the drug to reflect that the clinical benefit of ibrutinib for the treatment of CLL has been verified based on new trial results. These results confirmed the progression-free survival (PFS) and overall survival (OS) benefits associated with ibrutinib.
The expanded indication for patients with 17p deletion is based on a clinical trial of 391 previously treated patients with CLL; of these, 127 patients had CLL with 17p deletion. Participants were randomized to ibrutinib or to ofatumumab until disease progression or until side effects became intolerable.
The trial was stopped early after an interim analysis showed that patients receiving ibrutinib had a 78% improvement in PFS and a 57% OS benefit. Among the 127 patients with CLL plus 17p deletion, those receiving ibrutinib had a 75% improvement in PFS.
Ibrutinib was previously approved for the treatment of patients with mantle-cell lymphoma.