The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Treatment of chronic lymphocytic leukemia (CLL) with the combination of umbralisib plus ublituximab (U2) resulted in prolonged progression-free survival (PFS) compared with obinutuzumab plus chlorambucil, according to the results of the phase 3 UNITY-CLL study presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

“UNITY-CLL is the first randomized trial of a PI3Kδ inhibitor (umbralisib) in treatment-naive CLL, establishing a new mechanism of action in this treatment setting,” John G. Gribben, MD, DSc, FRCP, FMedSci, FRCPath, of Barts Cancer Institute in London, and presenter of the study, said.

The multicenter, phase 3 UNITY-CLL trial randomly assigned 421 patients with CLL requiring treatment to receive U2 or the chemoimmunotherapy (CIT) regimen, obinutuzumab plus chlorambucil. Patients could have treatment-naive or relapsed/refractory disease. The primary endpoint was PFS, and secondary endpoints included overall response rate (ORR), complete response (CR), undetectable minimal residual disease (uMRD), duration of response (DOR), and safety.

At baseline, the median age of patients was 68 years, 66% of patients were male, and 57% of patients were treatment-naive. Among the 43% of patients with relapsed/refractory CLL, the median number of prior therapies was 1 in the CIT group and 2 in the U2 group. High-risk features included 10% with del(17p), 20% with del(11q), and 55% with IGHV that was unmutated.


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The ORR with U2 was 83.3% compared with 68.7% with CIT. The ORR was similar when stratified by previous treatment in the U2 group, at 84% among treatment-naive patients compared with 82% among previously treated patients. For patients treated with CIT, the ORR was 78% and 57%, respectively. Patients treated with a prior BTK inhibitor had a lower ORR of 57% with U2 and 25% with CIT. Responses were maintained at 2 years among 62% of patients.

PFS was significantly prolonged with U2, with a median of 31.9 months compared with 17.9 months with CIT (hazard ratio [HR], 0.546; 95% CI, 0.413-0.720; P <.0001) during a median follow-up of 36.2 months. The 24-month PFS rate was 60.8% and 40.4% among patients treated with U2 and CIT, respectively. The PFS benefit was similar among most subgroups.

Among treatment-naive patients, the PFS was also longer with U2, with a median of 38.5  months compared with 26.1 months with CIT (HR, 0.482; 95% CI, 0.316-0.736; P <.001). PFS was generally shortened among patients with previously treated disease, but prolonged with U2 with a median of 19.5 months compared with 12.9 months with CIT (HR, 0.601; 95% CI, 0.415-0.869; P <.01).

The duration of exposure to treatment was substantially longer in the U2 group, with a median of 21 months compared with 5 months in the CIT group. The most common grade 3/4 adverse events (AEs) were neutropenia and diarrhea. Treatment discontinuation due to AEs occurred among 16.5% of patients treated with U2 and 7.6% of patients treated with CIT.

Dr Gribben concluded that these data suggest that U2 “is highly active in the treatment of CLL with demonstrated efficacy including prolonged PFS compared to CIT” and has a “well-tolerated safety profile.”

Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.

Reference

Gribben JG, Jurczak W, Jacobs R, et al. Umbralisib plus ublituximab (U2) is superior to obinutuzumab plus chlorambucil (O+Chl) in patients with treatment naive (TN) and relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL): results from the phase 3 Unity-CLL study. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-9, 2020. Abstract 543.