Credit: Steven Harbour
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia (CLL).
The agency previously granted the drug accelerated approval to treat CLL patients who had received at least 1 prior therapy.
Now, the FDA has granted ibrutinib full approval for that indication and expanded the drug’s approved use to include previously treated and untreated CLL patients with 17p deletion.
The FDA’s decision to grant ibrutinib accelerated approval in CLL was based on the drug’s ability to elicit responses in previously treated patients.
Recent trial results have shown the drug can improve survival rates in CLL, which signifies a clinical benefit and allows the FDA to grant ibrutinib full approval.
Ibrutinib in CLL: Trial results
The expanded approval for 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 in development
Ibrutinib is being studied alone and in combination with other treatments in several hematologic malignancies, including CLL, mantle cell lymphoma (MCL), Waldenstrom’s macroglobulinemia, diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma.
Before the FDA granted ibrutinib accelerated approval in CLL, the agency granted the drug accelerated approval for use in previously treated MCL patients. Studies to verify ibrutinib’s clinical benefit in MCL are ongoing.
The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended marketing authorization for ibrutinib to treat adults with relapsed or refractory MCL.
The committee has also recommended the drug for adults with CLL who have received at least 1 prior therapy and CLL patients with 17p deletion or TP53 mutation who cannot receive chemo-immunotherapy.
Ibrutinib is already approved in Israel for the treatment of adults with MCL who have received at least 1 prior therapy.
Ibrutinib is under development by Janssen Biotech and Pharmacyclics, Inc. The companies co-market ibrutinib in the US, but Janssen markets (or will market) ibrutinib in the rest of the world.
