FDA Approves Ibrutinib in Combination With Obinutuzumab in Treatment-Naive CLL/SLL
Today, the U.S. Food and Drug Administration (FDA) approved ibrutinib (Imbruvica), a Bruton's tyrosine kinase inhibitor, in combination with obinutuzumab in treatment-naive patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This is the first approval of a nonchemotherapy combination regimen for treatment-naive patients with CLL/SLL.
iLLUMINATE Trial
This approval is based on results from the phase III iLLUMINATE trial. At a median follow-up of 31 months, ibrutinib plus obinutuzumab showed 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] = 0.23; 95% confidence interval [CI] = 0.15–0.37; P< .0001), with a 77% reduction in risk of progression or death.
Patients with high-risk disease (17p deletion/TP53 mutation, 11q deletion, or unmutated immunoglobulin heavy chain variable region gene) treated with ibrutinib plus obinutuzumab experienced an 85% reduction in risk of progression or death (HR = 0.15; 95% CI = 0.09–0.27). The IRC-evaluated overall response rate was 89% in the ibrutinib-plus-obinutuzumab arm vs 73% in the chlorambucil-plus-obinutuzumab arm.
The data were recently presented in an oral session at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 691) and simultaneously published by Moreno et al in The Lancet Oncology.
Safety
Warnings and precautions with ibrutinib include hemorrhage, infections, cytopenias, cardiac arrhythmias, hypertension, second primary malignancies, tumor-lysis syndrome, and embryofetal toxicity. 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 were neutropenia (48%), thrombocytopenia (36%), rash (36%), diarrhea (34%), musculoskeletal pain (33%), bruising (32%), cough (27%), infusion-related reaction (25%), hemorrhage (25%), and arthralgia (22%).
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.
The FDA also updated the ibrutinib label to include additional long-term efficacy data supporting its use as a monotherapy in CLL/SLL, with approximately 5 years of follow-up from the phase III RESONATE and RESONATE-2 international studies.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
