Phase I study of duvelisib in Japanese patients with relapsed or refractory lymphoma
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ORIGINAL ARTICLE
Phase I study of duvelisib in Japanese patients with relapsed or refractory lymphoma Koji Izutsu1,2 · Koji Kato3 · Hitoshi Kiyoi4 · Go Yamamoto1 · Kazuyuki Shimada4 · Koichi Akashi3 Received: 12 March 2020 / Revised: 15 June 2020 / Accepted: 24 June 2020 © Japanese Society of Hematology 2020
Abstract Duvelisib is a novel dual inhibitor of phosphoinositide-3-kinase (PI3K)-δ and -γ. This single-arm, multicenter phase I study investigated its safety, pharmacokinetics, and preliminary efficacy in Japanese patients with relapsed or refractory lymphoma. Duvelisib was administered orally twice daily at 25 mg in 28-day cycles. Seven patients, comprising 4 with follicular lymphoma (FL), 2 with diffuse large B-cell lymphoma, and 1 with mantle cell lymphoma (MCL) were enrolled. No dose-limiting toxicity occurred in any patient. The most commonly experienced treatment-related adverse events of any grade were neutropenia and thrombocytopenia, occurring in 3 patients each (42.9%); followed by lymphopenia, diarrhea, enterocolitis, stomatitis, hepatic function abnormal, ALT increased, and AST increased, occurring in 2 patients each (28.6%). The most common grade ≥ 3 treatment-related adverse events were neutropenia, which occurred in 3 patients (42.9%), and thrombocytopenia, lymphopenia, and hepatic function abnormal, which occurred in 2 patients each (28.6%). One patient with FL achieved a complete response; the remaining 3 with FL and the 1 with MCL achieved a partial response. The overall response rate was 71.4% (5/7 patients). Duvelisib was well tolerated in Japanese patients with relapsed or refractory lymphoma. Safety and preliminary efficacy data support further development of duvelisib in Japanese patients. Keywords Clinical trial · PI3K · Japanese · Lymphoma · Duvelisib
Introduction Duvelisib is a novel dual inhibitor of phosphoinositide-3-kinase (PI3K)-δ and -γ. Phosphoinositide-3-kinase is a lipid kinase involved in intracellular signal transduction in many types of cell. The isoforms of its catalytic subunit (p110) exist as α, β, δ, and γ, with the δ and γ isoforms being preferentially expressed in leukocytes and involved in innate and adaptive immune function [1–4]. The pathways mediated by PI3K-δ and -γ contribute to survival, proliferation, * Koji Izutsu [email protected] 1
Department of Hematology, Toranomon Hospital, Minato‑ku, Tokyo, Japan
2
Department of Hematology, National Cancer Center Hospital, Chuo‑ku, 5‑1‑1 Tsukiji, Chuo‑ku, Tokyo 104‑0045, Japan
3
Department of Medicine and Biosystemic Science, Faculty of Medicine, Kyusyu University, Fukuoka, Japan
4
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
and differentiation of cancer cells in patients with advanced hematologic malignancies. Phosphoinositide-3-kinase-δ and -γ are also involved in the establishment and maintenance of the tumor microenvironment (TME), which plays an important role in the development and maintenance of cancer cells [5, 6]. Accordingly, we pre
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