The Food and Drug Administration has approved the supplemental New Drug Application (sNDA) for Imbruvica® (ibrutinib;Janssen) in combination with rituximab for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
The approval was based on data from the multicenter, open-label, phase 3 E1912 trial that compared the efficacy and safety of ibrutinib plus rituximab to fludarabine, cyclophosphamide and rituximab (FCR) in 529 adult patients aged ≤70 years with previously untreated CLL or SLL requiring systemic therapy. Patients were randomized 2:1 to receive ibrutinib plus rituximab (n=354) or FCR (n=175) until disease progression or unacceptable toxicity; those with 17p deletion were excluded from the study. The primary end point was progression free survival (PFS).
Findings from the trial showed that at 37 months, treatment with ibrutinib plus rituximab was associated with a statistically significant improvement in PFS when compared with the FCR arm (HR 0.34; 95% CI, 0.22-0.52; P <.0001). Additionally, results from a 48-month follow-up analysis showed continued PFS benefits with ibrutinib plus rituximab. Moreover, the combination demonstrated an improved overall survival benefit vs FCR at 48 months (HR 0.34; 95% CI, 0.15-0.79; P =.009).
With regard to safety, the most common adverse reactions (≥30%) in patients treated with ibrutinib for CLL/SLL were thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, and nausea. Treatment-related adverse events of Grade ≥3 occurred in 70% of patients in the ibrutinib plus rituximab arm compared with 80% in the FCR arm (OR 0.56; 95% CI, 0.34-0.90; P =.013).
Imbruvica, a Bruton’s tyrosine kinase inhibitor, is already indicated for the treatment of CLL/SLL with or without 17p deletion; Waldenström’s macroglobulinemia, previously treated patients with mantle cell lymphoma, previously treated patients with marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy, and previously treated patients with chronic graft-versus-host disease after failure of 1 or more lines of systemic therapy.
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