Ibrutinib Gains FDA Approval for CLL

Richard Pazdur, MD

The FDA has granted an accelerated approval to ibrutinib (Imbruvica) as a treatment for patients with chronic lymphocytic leukemia (CLL) who have received at least one previous therapy. Ibrutinib was initially approved as a treatment for patients with mantle cell lymphoma (MCL) in November 2013. The new indication is based on a single-arm clinical trial demonstrating a durable improvement in overall response rates (ORR).

“Today’s approval provides an important new treatment option for CLL patients whose cancer has progressed despite having undergone previous therapy,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The FDA completed its review of Imbruvica’s new indication under the agency’s accelerated approval process, which played a vital role in rapidly making this new therapy available to those who need it most.”

For the approval, the FDA focused specifically on 48 patients in the phase Ib/II PCYC-1102-CA study who received single-agent ibrutinib at 420 mg daily. In these select patients, at a median 15.6-month follow-up, the ORR was 58.3% (all partial responses) with duration of response of up to 24.2 months. The approval did not consider 34 patients enrolled in the trial who received daily ibrutinib at 840 mg; nor did it consider 3 patients with small lymphocytic lymphoma (SLL) who received the 420 mg dose, due to small sample size.

In this analysis, patients had received a median of 4 prior therapies and had a median age of 67 years. An independent review committee assessed this analysis. At this point, 85.4% of patients in the trial remained alive without progressive disease.

The most commonly occurring adverse reactions for patients with CLL in the PCYC-1102-CA trial were thrombocytopenia (71%), diarrhea (63%), bruising (54%), neutropenia (54%), anemia (44%), and upper respiratory tract infection (48%). The most common grade 3/4 non-hematological adverse reactions were pneumonia (8%), hypertension (8%), atrial fibrillation (6.3%), and sinusitis (6%). Additionally, ibrutinib-related grade 3/4 cytopenias were reported in 35% of patients. Altogether, 5 patients in the trial discontinued treatment due to adverse reactions.

"Rarely does a drug come along with so much potential to help CLL patients," said John C. Byrd, MD, the director of the Division of Hematology at the The Ohio State University Comprehensive Cancer Center and lead investigator of the PCYC-1102 trial. "I have been impressed with the promising and durable response rates we have seen in patients. It is particularly gratifying to see the difference that Imbruvica has made for patients in the clinical trials."

Ibrutinib is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. It is being explored as monotherapy in untreated patients with CLL and SLL in several settings. Additionally, the agent is under investigation in combinations with bendamustine and rituximab for patients with relapsed or refractory CLL.