The U.S. FDA granted breakthrough therapy designation for the investigational drug venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory CLL.
The drug is an inhibitor of the B-cell lymphoma-2 protein. In April 2015, single-agent venetoclax was granted breakthrough therapy designation for the treatment of relapsed/refractory CLL in patients with the del17p mutation.
The FDA’s decision was based in part on results from the phase II, open-label, single-arm, multicenter M13-982 study, which evaluated the safety and efficacy of venetoclax in 107 patients with relapsed/refractory or previously untreated CLL. The overall response rate was 79.4 percent among the patients receiving venetoclax and, at one-year, the rate of progression-free survival was 72 percent and the rate of overall survival was 86.7 percent.
The study also included a subset of 45 patients who were analyzed for the level of minimal residual disease (MRD) in peripheral blood and/or bone marrow. Among this cohort, 18 patients achieved MRD-negativity.
The most common treatment-related AEs included fever (7%), low red blood cell count as a result of immune response (7%), pneumonia (6%), and low white blood cell count with fever (5%). The most common grade 3/4 AEs were low white blood cell count (40%), low red blood cell count (18%), and low platelet count (15%). In addition, grade ≥3 infection occurred in 20 percent of patients.
Sources: Genentech press release, January 12, 2016; AbbVie press release, January 20, 2016.