Imbruvica plus Gazyva Approved as First-Line Treatment for CLL/SLL

April 2019, Vol 10, No 2 - FDA Approvals, News & Updates


On January 28, 2019, the FDA approved the combination of the oral Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica; Pharmacyclics), plus the CD20-directed cytolytic antibody obinutuzumab (Gazyva; Genentech), for the treatment of adults with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Imbruvica was already approved as a single agent for different indications, including for adults with CLL or SLL, with or without 17p deletion.

This latest approval was based on a phase 3, randomized, open-label, multicenter, clinical trial of 229 treatment-naïve patients with CLL or SLL, aged ≥65 years or those aged <65 years who had coexisting conditions, including creatinine clearance <70 mL/min and/or 17p deletion or TP53 mutation. The patients were randomized to ibrutinib plus obinutuzumab or to chlorambucil plus obinutuzumab; the primary end point was progression­free survival (PFS).

At a median follow-up of 31.3 months, the median PFS was significantly longer in the ibrutinib plus obinutuzumab group versus the chlorambucil plus obinutuzumab arm (the median PFS not yet reached vs 19 months). The estimated 30-month PFS was 79% (95% confidence interval [CI], 70-85) in the ibrutinib plus obinutuzumab arm versus 31% (95% CI, 23-40) in the chlorambucil plus obinutuzumab arm.

The most common (≥20%) adverse events with ibrutinib plus obinutuzu­mab were neutropenia, thrombocytopenia, rash, diarrhea, musculoskeletal pain, bruising, cough, infusion-related reaction, hemorrhage, and arthralgia.