Pembrolizumab in Japanese patients with primary mediastinal large B-cell lymphoma: results from the KEYNOTE-A33 study.

Autor: Kato K; Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan. kato.koji.429@m.kyushu-u.ac.jp., Nakamura S; MSD.K.K., 1-13-12 Kudan-Kita, Chiyoda-Ku, Tokyo, 102-0073, Japan., Wakana A; MSD.K.K., 1-13-12 Kudan-Kita, Chiyoda-Ku, Tokyo, 102-0073, Japan., Koh Y; MSD.K.K., 1-13-12 Kudan-Kita, Chiyoda-Ku, Tokyo, 102-0073, Japan., Izutsu K; National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Jazyk: angličtina
Zdroj: International journal of clinical oncology [Int J Clin Oncol] 2024 Dec; Vol. 29 (12), pp. 1977-1983. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1007/s10147-024-02627-8
Abstrakt: Background: KEYNOTE-A33 (NCT04317066) is an open-label, single-arm, phase 1 trial designed to evaluate the safety and efficacy of pembrolizumab in Japanese patients with relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBCL).
Methods: Patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary endpoints were safety and objective response rate (ORR) per International Working Group 2007 criteria by independent central review. The secondary endpoint was disease control rate (DCR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory.
Results: Seven patients were enrolled and treated; the median age was 32 years (range 26-43) and 86% were female. The median time from the first dose to data cutoff (April 12, 2022) was 5.6 months (range 2.4-21.2). Grade 3-5 treatment-related adverse events (AEs) occurred in 2 patients (29%; 2 grade 4 neutropenia, 1 grade 3 febrile neutropenia); however, no patient discontinued pembrolizumab or died because of treatment-related AEs. The ORR was 43% [95% confidence interval (CI) 10-82]. DCR was 57% (95% CI 18-90). Median DOR was not reached (NR). Four (57%) patients had a reduction in target lesion size of ≥ 50%. The median PFS was 2.9 months (95% CI 2.6-NR). The median OS was 17.5 months (95% CI NE-NE), and the 12 months OS rate was 100%.
Conclusion: Overall, pembrolizumab had manageable safety and clinically meaningful antitumor activity in Japanese patients with R/R PMBCL, results that were consistent with those observed in prior global studies.
Trial Registry: Registry and the Registration No. of the study/trial: Clinicaltrials.gov: NCT04317066.
Competing Interests: Declarations. Conflict of interest: Koji Kato reports honoraria from Bristol Myers Squibb, Celgene, Dainippon-Sumitomo, Janssen, Kyowa Kirin, MSD, Mundi, and Ono; consulting or advisory roles with AbbVie, AstraZeneca, Celgene, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Janssen, and Novartis; and research funding from AbbVie, Bristol Myers Squibb, Celgene, Chugai, Daiichi Sankyo, Eisai, Janssen, Kyowa Kirin, MSD, Novartis, and Ono. Sosuke Nakamura reports employment at MSD K.K., Tokyo, Japan. Akira Wakana reports employment at MSD K.K., Tokyo, Japan, and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. Yasuhiro Koh reports employment at MSD K.K., Tokyo, Japan, and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. Koji Izutsu reports research grants from AstraZeneca, AbbVie, Incyte, Bristol Myers Squibb, Novartis, Janssen, Chugai, BeiGene, and Genmab. This study was designed under the responsibility of, and was supported by, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and MSD.K.K., Tokyo, Japan, in conjunction with the steering committee. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and MSD.K.K., Tokyo, collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. Ethical approval: Ethical approval of the research protocol by an Institutional Review Board: The study protocol and all amendments were approved by the appropriate institutional review boards and ethics review committees at each center. The study was conducted in accordance with the protocol, Good Clinical Practice guidelines, and the Declaration of Helsinki. Informed consent: All patients provided written informed consent before enrollment.
(© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
Databáze: MEDLINE
Externí odkaz: