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Japanese phase Ib study of the oral PI3K-δ and -γ inhibitor duvelisib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma

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Abstract

This phase Ib, open-label, single-arm, multicenter study assessed the efficacy and safety of duvelisib, an oral dual inhibitor of phosphatidylinositol 3-kinase-δ and -γ, in Japanese patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Duvelisib was administered orally at 25 mg twice a day (BID) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and all responses were assessed by an independent review committee. Nine CLL patients and 1 SLL patient were enrolled. ORR was 80% (95% confidence interval 44.4, 97.5) for all 10 patients. All 6 patients previously treated with a Bruton’s tyrosine kinase (BTK) or BCL2 inhibitor achieved a partial response. The most common adverse events were neutropenia (50%), diarrhea (40%), anemia, hypokalemia, constipation and rash (30% each). The most common grade ≥ 3 adverse events were neutropenia (50%), anemia (30%) and thrombocytopenia (20%). Duvelisib 25 mg BID showed favorable efficacy and a manageable safety profile in selected Japanese patients with r/r CLL/SLL, including patients previously treated with BTK or BCL2 inhibitors (Clinical trial registration: jRCTs2080224791).

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Data availability

The data sets generated and analyzed in this study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was funded by Yakult Honsha Co., Ltd, and supported by Secura Bio, Inc. We would like to thank all the patients, investigators, and support staff who participated in this study. We are also grateful to Dr. Ukihide Tateishi and Dr. Sadao Aoki, Dr. Kensei Tobinai and Dr. Michinori Ogura, and Dr. Kiyohiko Hatake and Dr. Fumitaka Nagamura for their helpful advice as members of the independent review committee, medical experts, and members of the data monitoring committee, respectively. Yakult Honsha Co., Ltd. and Secura Bio, Inc. provided medical writing and editorial assistance.

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Authors and Affiliations

  1. Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Shinichi Makita & Koji Izutsu

  2. Department of Hematology, Sapporo Hokuyu Hospital, Hokkaido, Japan

    Shuichi Ota

  3. Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Yuko Mishima

  4. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan

    Kensuke Usuki

  5. Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan

    Daisuke Ennishi

  6. Department of Hematology and Cell Therapy, Aichi Cancer Center, Aichi, Japan

    Masamitsu Yanada

  7. Department of Hematology, Tohoku University Hospital, Miyagi, Japan

    Noriko Fukuhara

  8. Department of Hematology, Kobe City Medical Center General Hospital, Hyogo, Japan

    Ryusuke Yamamoto

  9. Pharmaceutical Research & Development Department, Yakult Honsha Co., Ltd., Tokyo, Japan

    Atsushi Takamine & Go Nohara

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  1. Shinichi Makita
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Correspondence to Shinichi Makita.

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Makita, S., Ota, S., Mishima, Y. et al. Japanese phase Ib study of the oral PI3K-δ and -γ inhibitor duvelisib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. Int J Hematol 119, 156–163 (2024). https://doi.org/10.1007/s12185-023-03689-6

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  • DOI: https://doi.org/10.1007/s12185-023-03689-6

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