Dermatologic Adverse Events in Patients Receiving Duvelisib Single-Agent and Combination Therapies

Duvelisib is a dual phosphoinositide 3 kinase (PI3K)-γ and -δ inhibitor currently approved for chronic lymphocytic leukemia and small lymphocytic lymphoma, with promise for T-cell lymphomas. Prior studies have characterized dermatologic adverse events (DAEs) associated with other PI3K inhibitors, but dedicated characterization of duvelisib-associated DAEs remains limited.

We retrospectively characterized possible, probable, or definite duvelisib-associated DAEs in 173 patients prescribed duvelisib primarily for T-cell lymphoma at our tertiary cancer center from 2000 to 2024.

DAE incidence was 31.9% (n = 23/72) on single-agent duvelisib, 18.6% (n = 8/43) on duvelisib-romidepsin, 17.4% (n = 4/23) on duvelisib-bortezomib, and 5.7% (n = 2/35) on duvelisib-ruxolitinib. Most DAEs were maculopapular rash (51.4%), xerosis (16.2%), or mucositis (8.1%), with 24.3% being grade 3 or higher. We noted a lower incidence of DAEs in patients treated with duvelisib combination regimens compared to single-agent duvelisib (P = .004), with patients on single-agent duvelisib being 2.9 times more likely (95% CI, 1.4-6.2) to develop DAEs. Patients on combination therapy were also less likely to discontinue duvelisib due to DAEs (P < .05). Separately, rash occurring after duvelisib discontinuation was observed in 5.8% of patients on any duvelisib combination (n = 10), most of which were maculopapular (60.0%) with one being a case of Stevens Johnsons Syndrome. Rashes occurred within a median of 4 days following duvelisib discontinuation.

Combining duvelisib with romidespin, bortezomib, or ruxolitinib reduced DAE incidence and allowed patients to remain on therapy. Further studies are required to delineate the effects of other agents on incidence and severity of PI3K inhibitor-associated DAEs.