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Effect of Dose Modifications on Response to Duvelisib in Patients with Relapsed/Refractory CLL/SLL in the DUO Trial

Conference Correspondent - ASCO 2019 - Chronic Lymphocytic Leukemia

Duvelisib, an oral, dual phosphoinositide 3-kinase (PI3K)-δ and PI3K-γ inhibitor, was approved in 2018 for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after 2 or more prior therapies. In the phase 3 DUO trial, duvelisib significantly improved efficacy versus ofatumumab in this patient population, with generally manageable toxicity. In this post hoc analysis, researchers examined dose-modification patterns and their impact on response to duvelisib in the DUO trial. The focus was on treatment-emergent adverse events of special interest, including infections, diarrhea, colitis, neutropenia, rash, and pneumonitis.

The recommended therapeutic dose of duvelisib is 25 mg administered orally twice daily. Dose interruptions or reductions to 15, 10, or 5 mg twice daily were permitted per study protocol to manage treatment-emergent adverse events. Among 158 patients treated with duvelisib, the median duration of duvelisib exposure was 11.6 months. Dose interruption occurred in 80% (N = 126) of patients, whereas dose reduction was required in 27% (N = 43) of patients. The most common cause of dose interruption was diarrhea/colitis, (28%), followed by infections (27%), cutaneous reactions (13%), neutropenia (12%), hepatotoxicity (6%), and pneumonitis (4%).

Among the 118 duvelisib responders, the median time to first response was 1.9 months and the median duration of response was 11.1 months. With duvelisib, the median time to first dose interruption was 4 months and the median duration was 14 days. Response to duvelisib was improved or maintained in most patients who had dose interruptions, although the percentage of responders decreased with longer interruptions.

In a landmark analysis, median progression-free survival was identical in patients with and without dose interruption for more than 7 days or more than 14 days (17.8 months vs 16.3 months) within the first 3 months of duvelisib treatment. The median time to dose reduction after achieving a complete or partial response was 5.6 months and the median duration was 3.4 months. The proportions of patients experiencing adverse events of special interest were stable or decreased over time, and duvelisib discontinuation rates were relatively low (≤10%).

The findings suggested that dose interruptions of 1 week or longer do not appear to significantly impact response to duvelisib in most patients.

Abstract 7523; Flinn I, et al.

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Last modified: June 4, 2019
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