Umbralisib Plus Ublituximab Prolongs PFS in Treatment-Naïve, Relapsed/Refractory CLL

Treatment with umbralisib plus ublituximab was associated with significant improvements in progression-free survival (PFS) compared with standard-of-care chemoimmunotherapy in patients with treatment-naïve and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), according to results from the phase III UNITY-CLL trial presented at the 62nd American Society of Hematology Annual Meeting & Exposition.

John Gribben, MD, of the Queen Mary University of London, and researchers, explained that umbralisib plus ublituximab has previously demonstrated promising activity and good tolerability in heavily pre-treated patients with CLL.

In the UNITY-CLL trial, a total of 421 treatment-naïve and R/R patients with CLL were randomly assigned to either oral umbralisib 800 mg once daily plus intravenous (IV) ublituximab 900 mg (n=210) or IV obinutuzumab 1,000 mg plus oral chlorambucil 0.5 mg/kg (n=211). The primary endpoint was PFS, and key secondary endpoints included overall response rate (ORR) and safety.

Overall, the median age of the study population was 67 years (range, 36-91 years). Approximately 57% of patients (n=240) were treatment-naïve, and 43% (n=181) presented to the study with R/R CLL.

After a median follow-up of 36.2 months, treatment with the umbralisib/ublituximab combination regimen was associated with significantly prolonged PFS compared with obinutuzumab and chlorambucil (median, 31.9 vs. 17.9 months, respectively; P<0.0001). The ORR, assessed by an independent review committee, was also higher with umbralisib plus ublituximab (83.3% vs. 68.7%; P<0.001).

Treatment discontinuation due to adverse events (AEs) was reported in 16.5% of patients on umbralisib plus ublituximab and 7.6% of patients on obinutuzumab and chlorambucil. Select grade 3/4 AEs of interest in both groups included neutropenia, thrombocytopenia, diarrhea, infusion related reaction, colitis, and pneumonitis (2.9% vs. 0%).