Ibrutinib plus rituximab approved by the FDA for frontline CLL/SLL

On April 21, 2020, the U.S. FDA approved the expanded indication of ibrutinib to be combined with rituximab for previously untreated adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The review was conducted under Project Orbis.¹

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase (BTK) inhibitor that interferes with BCR signaling and has proven effective in the treatment of patients with CLL. This new approval is based on the results from the phase III E1912 study (NCT02048813) that evaluated the efficacy of ibrutinib plus rituximab versus fludarabine, cyclophosphamide, and rituximab (FCR) in 529 newly diagnosed patients with CLL or SLL aged ≤70 years. This study demonstrated a statistically significant improvement in progression-free survival (PFS) in patients treated with ibrutinib plus rituximab compared with patients treated with FCR (HR 0.34; 95% CI, 0.22–0.52; p < 0.0001). At 37 months, PFS rate was 88% versus 75% in patients treated with ibrutinib plus rituximab and FCR, respectively.¹ The most common adverse reactions of all grades in patients treated with ibrutinib plus rituximab vs FCR were fatigue (80% vs 78%), musculoskeletal pain (61% vs 35%), and diarrhea (53% vs 27%).²

The extended follow-up results of the E1912 study were presented at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition and are available as part of a downloadable resource on the Lymphoma Hub.

Ibrutinib is currently indicated in five hematologic malignancies, including Waldenström's macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma.