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Hypomethylating agents, including azacytidine (AZA), are standard therapeutics for patients with high-risk myelodysplastic syndromes (MDS), a group of myeloid neoplasms. However, treatment schedules are not unified in real-world practice; in addition to the standard 7-day (standard-dose) schedule, shortened (reduced-dose) schedules are also used. The aim of this study was to discover the patient group(s) which show differential efficacy between standard-and reduced-dose AZA to MDS. The outcome of different AZA doses in a cohort of 151 MDS patients were retrospectively analyzed. Overall survival (OS) was not significantly different between standard- and reduced-dose AZA groups by multivariate analysis. However, an interaction was found between either the sex (female vs. male), the platelet counts (< 40 × 103 /μl vs. ≥ 40 × 103 /μl), or the karyotype risk (< poor vs. ≥ poor) and standard-dose AZA for longer OS. Subgroup analyses revealed better OS with standard- over reduced-dose AZA in female patients (HR, 0.27 [95% CI, 0.090-0.79]; p = 0.011), and those with platelet counts ≥ 40 × 103 /μl (HR, 0.51 [95% CI, 0.26-0.99]; p = 0.041). The union of female and preserved platelet count subgroups also benefited from standard-dose AZA. With this as a test cohort, we next analyzed patients registered in the JALSG MDS212 study, for whom 7-day and 5-day AZA treatment strategies were prospectively compared, as a validation cohort (N = 172). That cohort showed the same tendency as the retrospective results. We identified the union of female and preserved platelet count subgroups which benefited from standard-dose AZA, imparting crucial information to physicians planning treatment regimens in MDS patients. © 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.

Citation

Shinichi Ogawa, Tatsuhiro Sakamoto, Ryota Matsuoka, Kantaro Ishitsuka, Yasuko Ogino, Ayano Sootome, Kenichi Makishima, Chikashi Yoshida, Yufu Ito, Seiichi Shimizu, Takuya Suyama, Atsushi Shinagawa, Takayoshi Ito, Naoshi Obara, Manabu Kusakabe, Mamiko Sakata-Yanagimoto, Yasushi Miyazaki, Yasuhito Nannya, Shigeru Chiba. Female and preserved platelet count subgroups of myelodysplastic syndrome patients benefit from standard-dose azacitidine. Cancer reports (Hoboken, N.J.). 2024 Jan;7(1):e1938

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PMID: 38014499

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