The addition of a novel monoclonal antibody to ibrutinib significantly improves survival outcomes for patients with previously treated high-risk chronic lymphocytic leukemia (CLL), according to the results of a phase III GENUINE trial (NCT02301156).
Results come following similar outcomes reported in a prior phase II investigation. In this trial, 41 patients underwent combination therapy with a new drug – ublituximab – plus ibrutinib. The combination produced favorable overall response rates (ORR), response times, and nodal reductions, along with limited adverse events.
Jeffrey Sharman, MD, medical director for hematology research, US Oncology Network, and colleagues, conducted a phase III, open label study to further assess the efficacy and safety of ublituximab plus ibrutinib in a larger sample size of patients with high-risk CLL. A total of 126 patients who had received at least 1 prior therapy were randomized to receive either ibrutinib alone (n = 58) or in combination with intravenous ublituximab (n = 59). Ibrutinib was given once daily (420 mg) and ublituximab was administered (900 mg) on days 1, 8, and 15 during the first cycle and then on day 1 alone for cycles 2 through 6.
High-risk was defined as having 17p deletion, 11q deletion, or p53 deletion. The primary outcome was ORR and secondary outcomes included radiographic complete response, progression-free survival (PFS), and median time to response.
Results of the study showed an 80% ORR for patients receiving ublituximab plus ibrutinib compared with a 47% ORR for ibrutinib alone (P < .001). The combination was well tolerated with no new safety concerns. Data regarding adverse events are to be released at an upcoming medical meeting.
The combination of ublituximab plus ibrutinib also improved secondary outcomes. Patients receiving the combination therapy demonstrated improvements in radiographic complete response, PFS, and time to response compared with patients receiving ibrutinib alone.
"We believe that the rapid responses seen in our phase II study with ublituximab plus ibrutinib are validated here in our phase III GENUINE study and are important markers of improved overall efficacy and patient outcomes," said Dr Sharman.
Further studies are assessing ublituximab in combination with other therapies for patients with various hematological malignancies. – Zachary Bessette