FDA Approves Ibrutinib for Chronic Lymphocytic Leukemia

The US Food and Drug Administration (FDA) has approved ibrutinib (Imbruvica) as a single-agent treatment for previously treated patients with chronic lymphocytic leukemia (CLL), under the FDA’s accelerated approval program. CLL is a slow-progressing cancer of the lymphocytes, typically B-cells, and the most common adult form of leukemia.

Ibrutinib is a first-in-class oral drug that targets the Bruton’s tyrosine kinase (BTK) protein, and inhibits B-cell signaling and the survival of malignant B-cells. The drug was approved by the FDA for treatment of mantle-cell lymphoma in November 2013 under the FDA’s Breakthrough Therapy Designation program, which aims to accelerate the development and review of promising agents for life-threatening diseases. Ibrutinib also received an orphan drug designation from the FDA.

The approval is based on results of the international open-label, single-arm phase 1b/II PCYC-1102-CA clinical trial that consisted of 48 patients with relapsed or refractory CLL.

Efficacy results showed an overall response of 58.3% (all were partial responses). The duration of therapy ranged from 5.6 months to over 24.2 months, and the duration of response has not yet been reached. Most patients on the trial were diagnosed with CLL 6.7 years before starting the study and had received four prior therapies. Whether ibrutinib improves survival is not yet clear.

The recommended dose is 420 mg once daily.

The prescribing label warnings include potential of hemorrhage, infections, myelosuppression, renal toxicity, second primary malignancies, and embryo-fetal toxicity. Commonly experienced adverse events include thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, and pyrexia, among others. Thirteen percent of patients in the trial had adverse events that needed a dose reduction.

In the United States, it is estimated that about 15,680 patients per year are newly diagnosed with CLL and about 114,500 patients are living with CLL, a disease that is mostly diagnosed in the elderly, according to the National Cancer Institute. The 5-year survival rate of CLL is 82%.

A larger phase III CLL trial, called RESONATE, consisting of 391 relapsed or refractory CLL patients was stopped early in January because an interim analysis showed a significant improvement in progression-free survival in patients treated with ibrutinib compared with those treated with the CD20 antibody ofatumumab.