Ibrutinib in CLL: Indication Expanded, Benefit Confirmed

Zosia Chustecka


July 28, 2014

Ibrutinib (Imbruvica, Pharmacyclics), hailed as a "turning point" in the treatment for chronic lymphocytic leukemia (CLL), has just had another indication and a label change approved by the US Food and Drug Administration (FDA).

Ibrutinib was granted accelerated approval for use in CLL earlier this year, in February, on the basis of overall response rate. Since then, clinical trial data on progression-free survival and overall survival have "confirmed the drug's clinical benefit," the agency said. Hence, it has approved a labelling change to reflect the fact that the "clinical benefit in treating CLL has been verified."

In addition, the FDA has expanded the indication to include treatment of patients with CLL who carry a deletion in chromosome 17 (17p deletion), which is associated with poor responses to standard treatment for CLL. Ibrutinib had a breakthrough therapy designation for this use (but not for the previous indication of use in CLL), and the FDA notes that it completed the assessment for this indication 2 months ahead of schedule.

Ibrutinib also has an accelerated approval for use in mantle cell lymphoma in patients who had received at least 1 prior therapy, an indication for which it was also granted breakthrough therapy designation; that approval was granted in November 2013. Clinical studies to verify and describe Imbruvica's clinical benefit in mantle cell lymphoma are ongoing, the agency said.

"We continue to see advances in the availability of therapies to treat chronic lymphocytic leukemia, especially for difficult-to-treat patient populations," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research. He noted that ibrutinib is the fourth drug approved to treat CLL that received a breakthrough therapy designation; the others were obinutuzumab (Gazyva) in November 2013, ofatumumab (Arzerra) in April, and, just a few weeks ago, idelalisib (Zydelig), in July.

New Indication of CLL With 17p Deletion

The new indication for ibrutinib for CLL with 17p deletion is based on results from a subgroup of 127 patients with this abnormality from the RESONNATE clinical trial, which enrolled a total of 391 patients. These patients had progressed on previous therapies and were randomly assigned to receive either ibrutinib or ofatumumab.

The trial was stopped early for efficacy, as reported by Medscape Medical News, after a preplanned interim analysis showed that ibrutinib-treated participants experienced a 78% reduction in the risk for disease progression and a 57% reduction in the risk for death in the overall patient population, the FDA noted.

For the subgroup of 127 patients who had CLL with 17p deletion, those treated with ibrutinib experienced a 75% reduction in risk for disease progression or death, the agency said.

The most common adverse effects associated with ibrutinib observed in the clinical study included thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, upper respiratory tract infection, rash, nausea, and pyrexia, the FDA noted.


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