On January 28, 2019, the FDA approved the combination of ibrutinib (Imbruvica; Pharmacyclics), an oral Bruton’s tyrosine kinase inhibitor, plus obinutuzumab (Gazyva; Genentech), a CD20-directed cytolytic antibody, for the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Imbruvica has been previously approved as a single agent for the treatment of adults with CLL or SLL, including those with 17p deletion [del(17p)].
This latest approval was based on a phase 3, randomized, open-label, multicenter, clinical trial of 229 patients with previously untreated CLL or SLL who were aged ≥65 years or <65 years with co-existing conditions (Cumulative Illness Rating Scale score >6, creatinine clearance <70 mL/min, and/or del(17p) or TP53 mutation). Patients were randomized in a 1:1 ratio to ibrutinib plus obinutuzumab or chlorambucil plus obinutuzumab, with a primary end point of progression-free survival (PFS).
At a median follow-up of 31.3 months, median PFS, the primary end point of the study, was significantly longer in the ibrutinib plus obinutuzumab group (median not reached; 95% confidence interval [CI], 33.6; nonestimable) versus the chlorambucil plus obinutuzumab group (median 19.0 months; hazard ratio, 0.23; 95% CI, 0.15-0.37; P <.0001). The estimated 30-month PFS was 79% in the ibrutinib plus obinutuzumab group versus 31% in the chlorambucil plus obinutuzumab group.
The most common (≥20%) adverse events reported with ibrutinib plus obinutuzumab were neutropenia, thrombocytopenia, rash, diarrhea, musculoskeletal pain, bruising, cough, infusion-related reaction, hemorrhage, and arthralgia.