FDA Approves Ibrutinib/Obinutuzumab for Treatment-Naive Patients with Chronic Lymphocytic Leukemia

The US Food and Drug Administration (FDA) has approved Janssen’s ibrutinib plus obinutuzumab for treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

This approval serves as the first non-chemotherapy combination regimen for this patient population and ibrutinib’s 10^th approval for 6 different disease areas.

"In just a few years, ibrutinib has become an important treatment for chronic lymphocytic leukemia. Ibrutinib as a single agent—and now as a combination with obinutuzumab—provides patients with CLL with an alternative to frontline treatment with chemoimmunotherapy," said Carol Moreno, MD, PhD, Consultant Hematologist, Hospital de la Santa Creu Sant Pau, Autonomous University of Barcelona, Barcelona, Spain, and lead investigator of the iLLUMINATE study in a recent statement.

Results from the phase 3 iLLUMINATE study served as the basis for approval. Ibrutinib plus obinutuzumab demonstrated a significant improvement in Independent Review Committee (IRC)-evaluated progression-free survival compared with chlorambucil plus obinutuzumab (median not evaluable [NE] vs. 19 months; hazard ratio [HR] .23; 95% confidence interval [CI]: .15-.37; P<.0001), with a 77% reduction in risk of progression or death at a median follow-up of 31 months.

Patients treated with ibrutinib plus obinutuzumab who were with high-risk disease disease (17p deletion/TP53 mutation, 11q deletion, or unmutated IGHV) experienced an 85% reduction in risk of progression or death (HR .15; 95% CI: .09-.27).

In the ibrutinib plus obinutuzumab arm, the IRC-evaluated overall response rate was 89% compared to 73% in the chlorambucil plus obinutuzumab arm.

Hemorrhage, infections, cytopenias, cardiac arrhythmias, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity include the warnings and precautions with ibrutinib plus obinutuzumab.

Neutropenia (48%), thrombocytopenia (36%), rash (36%), diarrhea (34%), musculoskeletal pain (33%), bruising (32%), cough (27%), infusion related reaction (25%), hemorrhage (25%), and arthralgia (22%) included the most common adverse reactions (occurring in 20% or more of patients) of all grades in patients treated with ibrutinib plus obinutuzumab in the iLLUMINATE study.

The recommended dose for ibrutinib plus obinutuzumab 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 (BR). Physicians should consider administering ibrutinib prior to rituximab or obinutuzumab when given on the same day when administering ibrutinib in combination with rituximab or obinutuzumab.

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