Dermatologic adverse events in patients receiving duvelisib single-agent and combination therapies

Summary: Abstract Body: Duvelisib is a dual phosphoinositide 3 kinase (PI3K)-g and -d inhibitor, approved for chronic and small lymphocytic leukemia, that is a promising treatment for T-cell lymphomas. Dermatologic adverse events (DAEs) associated with duvelisib have been observed in hematologic malignancy clinical trials and reported in the product's prescribing information, although no in-depth assessment on these has been performed. We retrospectively characterized possible, probable, or definite duvelisib-associated DAEs in all 173 patients treated with duvelisib at our tertiary cancer center from 2000-2024. DAE incidence while on duvelisib was 31.9% (23/72) on single agent duvelisib, 18.6% (8/43) on duvelisib and romidepsin, 17.4% (4/23) on duvelisib and bortezomib, and 5.7% (2/35) on duvelisib and ruxolitinib. Across all regimens, most DAEs were maculopapular rash (n=19, 51.4%), xerosis (n=6, 16.2%), or mucositis (n=3, 8.1%). 24.3% (n=9) were grade 3 DAEs. For single agent duvelisib, median time to DAE onset was 78 days and median duration 29 days. Single agent duvelisib DAEs were managed with topical steroids (56.5%), antihistamines (26.1%) or systemic steroids (34.8%). Most patients (73.9%) continued duvelisib. In addition, 11 patients (6.4%) developed rash only after duvelisib was discontinued for another indication, mostly appearing as maculopapular rash (63.6%) within median 3 days. Our data is consistent with published PI3Ki DAE incidence rates as well as information and management recommendations in the approved labeling for duvelisib. We noted a lower incidence of DAEs (p=.004) and fewer patients with severe DAEs (p=.04), trending towards shorter duration DAE (p=.08), in patients on duvelisib in combination with romidepsin, bortezomib or ruxolitinib compared to patients on duvelisib alone. Further studies are required to delineate the effects of other agents on incidence and severity of PI3Ki-associated DAEs. Viviane Liao¹, Nivetha Ganesan², Stephen Dusza¹, Steven Horwitz², Alison Moskowitz², Shamir Geller¹ 1. Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States. 2. Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States. Clinical Research: Interventional Research