Idelalisib Approved for Trio of Blood Cancers

Foster City, CA–based Gilead received approval for idelalisib (Zydelig) on July 23 for the treatment of relapsed chronic lymphocytic leukemia (CLL), follicular B-cell non-Hodgkin lymphoma (FL), and small lymphocytic lymphoma (SLL). These cancers affect more than 200,000 Americans, according to Gilead.

Idelalisib is an oral inhibitor of PI3K delta, a protein critical for the activation, proliferation, and survival of B-cells in lymphoid tissues.

For CLL, the drug was approved for use in combination with rituximab (Rituxan; Genentech) in patients for whom rituximab alone would be considered appropriate treatment. The approval was based on a phase III trial of 220 patients with relapsed CLL who were not eligible for chemotherapy.

The study, published earlier this year in The New England Journal of Medicine, was stopped early after an interim analysis showed that median progression-free survival reached at least 10.7 months in patients treated with idelalisib plus rituximab compared with 5.5 months with rituximab alone. In addition, 81% of idelalisib-treated patients responded to therapy versus only 13% in the rituximab-alone arm.

“The majority of patients remain on the drug and continue to respond,” says lead investigator Richard Furman, MD, director of the CLL Research Center at Weill Cornell Medical College in New York, NY. The study started in May 2012.

The FDA granted accelerated approval of idelalisib for FL and SLL based on a single-group phase II study that showed overall response rates of 54% and 58%, respectively. The drug is intended for FL and SLL patients who have received at least two prior systemic therapies.

Idelalisib is the second targeted drug approved in 2014 for relapsed CLL. In February, the FDA approved ibrutinib (Imbruvica; Janssen Biotech and Pharmacyclics), an oral inhibitor of Bruton's tyrosine kinase, for patients with CLL who have received at least one prior therapy. Idelalisib and ibrutinib are currently being studied as first-line treatments for CLL.

Idelalisib will carry a boxed warning about potentially fatal liver toxicity, severe diarrhea or colitis, pneumonitis, and intestinal perforation. The FDA approved a risk evaluation and mitigation strategy to inform healthcare providers about these risks. The most common side effects include diarrhea, fever, fatigue, nausea, and cough.

John Byrd, MD, hematology division director at Ohio State University Comprehensive Cancer Center in Columbus, anticipates that more patients with CLL will receive ibrutinib before idelalisib. “The data look stronger with ibrutinib in terms of the duration of response and the toxicity profile,” says Byrd, who led the phase III testing of ibrutinib in CLL.

With the earlier approval of ibrutinib and now idelalisib—and the many promising targeted agents in clinical trials—Byrd says he rarely uses chemotherapy. “We're rapidly heading toward a chemotherapy-free treatment approach for CLL,” he says.