Dr. Sharman on the Results of the GENUINE Trial in CLL

Jeff P. Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses the results of the phase 3 GENUINE trial in chronic lymphocytic leukemia (CLL).

In GENUINE, investigators evaluated the addition of ublituximab to ibrutinib (Ibruvica) in previously treated patients with high-risk relapsed/refractory CLL. Due to low enrollment, the trial protocol was amended to evaluate overall response rate (ORR) as a primary end point and progression-free survival (PFS) as a secondary end point, says Sharman.

The results, which were presented during the 2020 ASCO Virtual Scientific Program, showed a statistically significant improvement in ORR with the addition of ublituximab. Notably, ORR may not be an important end point as it relates to BTK inhibition, which tends to lead to more prolonged responses, explains Sharman. PFS also favored the combination. Patients with 11q deletion, which confers lower risk, did not benefit as much as those with known poor prognostic features, such as TP53 mutations and 17p deletions, adds Sharman. GENUINE is the first randomized trial to demonstrate a PFS benefit with the addition of a CD20-directed antibody to ibrutinib. However, the necessity of adding CD20-directed antibodies to BTK inhibitors remains unclear, concludes Sharman.