The new combination treatment of ublituximab plus ibrutinib resulted in a higher overall response rate and a tolerable safety profile for patients with relapsed or refractory high-risk CLL.
The combination of ublituximab plus ibrutinib (Imbruvica) led to a statistically higher overall response rate while maintaining the tolerable safety profile over ibrutinib monotherapy to treat patients with relapsed or refractory high-risk chronic lymphocytic leukemia (CLL).
According to data published in The Lancet Haematology from the phase 3, multicenter, GENUINE (NCT02301156) trial, these findings support the addition of ublituximab to Bruton tyrosine kinase (BTK) inhibitors as treatment for patients with this class of CLL.
“Clinically meaningful improvements in overall response rate, complete response, and MRD negative response were observed and translated into improved progressionfree survival,” wrote the investigators. “These findings indicate the benefit of adding the nextgeneration antiCD20 antibody ublituximab to ibrutinib in patients with relapsed and refractory high-risk chronic lymphocytic leukaemia.”
The overall response rate was 83% of patients in the ublituximab plus ibrutinib group and 65% of patients in the ibrutinib group (P = .020) after a median follow-up of 41.6 months (IQR 36.7–47.3).
While the safety profile consisted mostly of grade 1 or 2 adverse events, neutropenia (19% of patients in the combination group vs 12% in the control group), anemia (8% vs 9%, respectively), and diarrhea (10% vs 5%) were common grade 3 and 4 adverse events among the population of interest.
More, common serious adverse events included pneumonia (10% with ublituximab vs 7% with ibrutinib only), atrial fibrillation (7% vs 2%, respectively), sepsis (7% vs 2%), and febrile neutropenia (5% vs 2%).
Two patients from the ublituximab plus ibrutinib group and 5 patients and from the ibrutinib group died from adverse events. Only 1 death (cardiac arrest) from the ibrutinib group was considered treatment-related.
“Ublituximab plus ibrutinib was generally well tolerated,” wrote the investigators. “With the exception of infusionrelated reactions associated with ublituximab, the combination therapy did not greatly alter the known safety profile of singleagent ibrutinib; however, a higher rate of neutropenia was observed in the ublituximab plus ibrutinib group.”
Between February 6, 2015, and December 19, 2016, a total of 126 patients were enrolled and randomly assigned for treatment, with 64 patients to the ublituximab plus ibrutinib group and 62 patients to the ibrutinib group.
The safety profile was drawn from a population of 117 patients, with 59 patients from the ublituximab plus ibrutinib group and 58 patients from the ibrutinib group. These patients underwent at least 1 dose of treatment in their respective groups.
A main limitation of the research is that the research was mostly done at community centers, likely slowing down the process of identifying eligible patients. More, the needed commercial acquisition of ibrutinib introduced accessibility issues for eligible patients, limiting the potential for study expansion.
“These results highlight the need for further randomised studies on ways to improve long-term progression-free survival, overall response rate, and minimal residual disease negativity in patients with high-risk chronic lymphocytic leukaemia treated with ibrutinib, and, specifically, the role of next-generation anti-CD20 therapies in this setting,” wrote the investigators. “The results also suggest that such benefits might be subgroup-specific.”
Sharman JP, Brander DM, Mato AR, et al. Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial. Lancet Haematol. February 22, 2021. doi:10.1016/ S2352-3026(20)30433-6