FDA Approves Ibrutinib as First-Line CLL Treatment

March 9, 2016

The FDA recently approved ibrutinib (Imbruvica) for initial treatment of chronic lymphocytic leukemia (CLL), the first chemotherapy-free treatment option approved by the agency for first-line CLL patients.

The US Food and Drug Administration (FDA) recently approved ibrutinib (Imbruvica) for initial treatment of chronic lymphocytic leukemia (CLL), the first chemotherapy-free treatment option approved by the agency for first-line CLL patients.

“This approval represents a significant leap forward for patients diagnosed with CLL who may want to consider an alternative first-line treatment to traditional chemotherapy,” said Michael Severino, MD, executive vice president of research and development, and chief scientific officer, in an Abbvie press release.    

The approval was based on findings from the randomized, multicenter, open-label phase III RESONATE-2 (PCYC-1115) clinical trial, which compared ibrutinib versus the chemotherapy drug chlorambucil (Leukeran) among 269 elderly, treatment-naïve patients diagnosed with CLL or small lymphocytic lymphoma (SLL). Study findings were presented at the December 2015 American Society of Hematology (ASH) annual meeting and published in The New England Journal of Medicine.

The study revealed an 84% reduction in the risk of CLL progression or death among patients in the ibrutinib study group compared to the control group (hazard ratio [HR] 0.161; 95% CI: 0.091-0.283; P = .001; median progression-free survival [PFS]: not reached vs 18.9 months for control). Overall response rates (ORR) were also superior among patients in the ibrutinib group (82.4% vs 35.3%; P < .0001).

Sustained hemoglobin and platelet level increases were higher among patients administered ibrutinib than those in the control group.

The most common adverse events among patients in the ibrutinib group included diarrhea, fatigue, cough, and nausea. Five patients in the ibrutinib group experienced hemorrhage; three of these cases were grade 3 and one was a grade 4 hemorrhage.

An estimated 115,000 US patients live with CLL, and 15,000 more are diagnosed each year. The average age at diagnosis is 71 years.

Ibrutinib is a first-in-class oral once-daily agent that inhibits production of Bruton’s tyrosine kinase (BTK), a signaling protein involved in B-cell survival. It is now approved for CLL treatment for patients without regard to their treatment histories, the company noted in a press release.

Ibrutinib was previously approved for high-risk CLL patients with deletion 17p, a genetic mutation that affects tumor suppressor gene p53, and for patients diagnosed with CLL or mantle cell lymphoma with prior treatment histories. It was one of the first drugs approved under the FDA’s Breakthrough Therapy Designation program.