FDA Approves Ibrutinib as First-Line Treatment for Chronic Lymphocytic Leukemia

Ibrutinib (Imbruvica) is the first chemotherapy-free treatment for first line CLL patients approved by the FDA.

The FDA today approved ibrutinib (Imbruvica) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).

This approval came followed the phase 3 RESONATE-2 (PCYC-1115) trial, which enrolled 269 treatment naïve patients suffering from CLL or small lymphocytic lymphoma (SLL). Patients had to be 65 years or older and live within the United States, Europe, and other regions.

Patients were randomized to receive either a daily dose of Imbruvica 420 mg orally until progression or high toxicity, or chlorambucil on days 1 and 15 on each 28 day cycle for up to 12 cycles.

An assessment by an independent review committee found that imbruvica significantly improved progression free survival (PFS) by 84% compared with chlorambucil (hazard ratio [HR], 0.161 [95% confidence interval: 0.091, 0.283]. The median PFS primary endpoint was not reached for Imbruvica compared with 18.9 months with chlorambucil.

Furthermore, Imbruvica had a signicantly higher overall response rate compared with chlorambucil (82.4% vs. 35.3%; P<0.0001). There were also 5 patients who were able to achieve a complete response in the Imbruvica group versus 2 patients in the chlorambucil group.

The most common adverse events were diarrhea, musculoskeletal pain, cough, and rash.

"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 Executive Vice President of AbbVie, Michael Severino, MD. "AbbVie is committed to making significant improvements in the lives of patients with hematologic malignancies and will continue to explore ways to improve treatment options for patients."

Currently, there are more than 115,000 patients living with CLL, and 15,000 newly diagnosed patients each year. The average age of diagnosis is 71-years-old.

Recently the National Comprehensive Cancer Network (NCCN) published an update on its clinical practice guidelines for those with non-Hodgkin’s lymphomas. Imbruvica was granted a category 1 recommendation for certain CLL patients.

NCCN recommends that Imbruvica be used as a first-line treatment option for frail CLL patients that have significant comorbidities and CLL patients 70 years and older with or without del 17p or TP53, as well as younger patients with comorbidities.

"The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging," said RESONATE-2 lead study investigator, Jan Burger, MD, PhD. "This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients."