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Umbralisib Associated With a Better Safety Profile Than Other PI3K Inhibitors
The use of single-agent umbralisib in adults with relapsed or refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), is associated with a favorable tolerability profile, including low rates of serious immune-mediated toxicities.
“The favorable safety profile of umbralisib is particularly relevant for patients with indolent NHL, many of whom have a chronic history that often requires ongoing treatment for prolonged periods,” wrote lead author Matthew S. Davids, MD, department of Medical Oncology, Dana-Farber Cancer Institute, Boston, and co-authors.
The researchers analyzed combined data from 371 patients with R/R NHL (follicular lymphoma [FL], n = 147; marginal zone lymphoma [MZL], n = 82; DLBCL/mantle cell lymphoma [MCL], n = 74; chronic lymphocytic leukemia [CLL], n = 43; and other tumor types, n = 25) who participated in 4 open-label, phase 1 and 2 clinical trials as of September 1, 2019.
Patients received umbralisib for a median duration of 5.9 months (range, 0.1-75.1 months), with 92 (24.8%) of 371 patients receiving treatment from 12 to less than 24 months, and 15 (4%) of 371 patients receiving treatment of 24 months or more.
The most common treatment-emergent adverse events (TEAEs) for patients treated with umbralisib for less than 1 year (n = 107) were diarrhea (60.7%), neutropenia (17.8%), AST increase (16.8%), and ALT increase (15%). Grade 3 or higher TEAEs occurred in 189 (50.9%) of 371 patients. The most common grade 3 or higher TEAEs included neutropenia (11.3%), diarrhea (7.3%), and an increase in certain liver enzymes (ALT or AST; 5.7%).
About one-third of patients treated with umbralisib experienced a grade 3 or higher TEAE attributed to umbralisib. The most common of these were neutropenia (8.9%), diarrhea (6.7%), and increased aminotransferase levels (5.4%). These rates are substantially lower than those reported for other PI3K inhibitors in similar patient populations.
In the current analysis, 13.7% of patients discontinued treatment due to AEs, which seems to be favorable in light of the 20%, 25%, and 52% discontinuation rates due to AEs in clinical trials of idelalisib, copanlisib, and duvelisib, respectively.
