FDA Approves Ibrutinib Combo Regimen for CLL

Officials with the FDA have approved ibrutinib (Imbruvica) in combination with obinutuzumab for treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), representing the tenth FDA approval for ibrutinib, according to a press release.

With this approval, ibrutinub plus obinutuzumab becomes the first FDA-approved non-chemotherapy combination regimen for this patient population. Ibrutinib, a once-daily oral Bruton’s tyrosine kinase inhibitor, was previously approved for the treatment of CLL/SLL as a monotherapy in 2016. Ibrutinib’s label now includes additional monotherapy long-term follow-up data.

CLL is the most common form of leukemia in adults. CLL and SLL are essentially the same disease, with the only difference being the location where the cancer primarily occurs. In 2019, there will be an estimated 20,720 new cases of CLL and an estimated 3930 deaths from the disease, according to the American Cancer Society.

The approval is based on data from the phase 3 iLLUMINATE clinical trial. The study evaluated the combination therapy compared with chlorambucil plus obinutuzumab in previously untreated patients with CLL or SLL. Patients received either ibrutinib 420 mg continuously in combination with obinutuzumab 1000 mg intravenously over 6 cycles or chlorambucil on days 1 and 15 of each cycle plus obinutuzumab.

According to the results, ibrutinib plus obinutuzumab showed a significant improvement in progression-free survival as evaluated by the Independent Review Committee (IRC) compared with chlorambucil plus obinutuzumab at a median follow-up of 31 months. Treatment with ibrutinib plus obinutuzumab also reduced the risk of progression or death by 77%. In patients with high-risk disease, ibrutinib plus obinutuzumab reduced the risk of progression or death by 85% and the IRC-evaluated overall response rate was 89% versus 73% in the chlorambucil plus obinutuzumab arm, according to the study.

The recommended dose of ibrutinib for CLL/SLL is 420 mg orally once daily until disease progression or unacceptable toxicity as a single agent or in combination with obinutuzumab or bendamustine and rituximab. If given in a combination regimen, the physicians should consider administering ibrutinib prior to rituximab or obinutuzumab when given on the same day, according to Janssen.

“This label update builds upon established efficacy and safety of Imbruvica in the frontline treatment of patients with CLL/SLL, as a monotherapy or in combination with other treatments,” Craig Tendler, MD, vice president, Clinical Development and Global Medical Affairs, Janssen Research and Development, said in a statement. “This milestone represents our continued commitment to develop Imbruvica-based, non-chemotherapy regimens to address the clinical needs of patients living with CLL/SLL.”

Ibrutinib is jointly developed and commercialized by Janssen Biotech and Pharmacyclics, an AbbVie company.

Reference

US FDA Approves Imbruvica (ibrutinib) Plus Obinutuzumab as First Non-Chemotherapy Combination Regimen for Treatment-Naïve Patients with Chronic Lymphocytic Leukemia [news release]. Janssen’s website. https://www.janssen.com/us-fda-approves-imbruvica-ibrutinib-plus-obinutuzumab-first-non-chemotherapy-combination-regimen. Accessed January 28, 2019.