Considerations for Drug Development in Myelodysplastic Syndromes.

Autor:	Sekeres MA; Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida., Kim N; NCI, NIH, Bethesda, Maryland., DeZern AE; Johns Hopkins University, Baltimore, Maryland., Norsworthy KJ; Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland., Garcia JS; Dana-Farber Cancer Institute, Boston, Massachusetts., de Claro RA; Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland., Theoret MR; Oncology Center of Excellence, FDA, Silver Spring, Maryland., Jen EY; Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland., Ehrlich LA; Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland., Zeidan AM; Section of Hematology, Department of Internal Medicine, Yale School of Medicine, and Yale Cancer Center, Yale University, New Haven, Connecticut., Komrokji RS; H. Lee Moffitt Cancer Center, Tampa, Florida.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Jul 14; Vol. 29 (14), pp. 2573-2579.
DOI:	10.1158/1078-0432.CCR-22-3348
Abstrakt:	Myelodysplastic syndromes (MDS) have historically been challenging diseases for drug development due to their biology, preclinical modeling, and the affected patient population. In April 2022, the FDA convened a panel of regulators and academic experts in MDS to discuss approaches to improve MDS drug development. The panel reviewed challenges in MDS clinical trial design and endpoints and outlined considerations for future trial design in MDS to facilitate drug development to meaningfully meet patient needs. Challenges for defining clinical benefit in patients with MDS include cumbersome response criteria, standardized transfusion thresholds, and application and validation of patient reported outcome instruments. Clinical trials should reflect the biology of disease evolution, the advanced age of patients with MDS, and how patients are treated in real-world settings to maximize the likelihood of identifying active drugs. In patients with lower-risk disease, response criteria for anemic patients should be based on baseline transfusion dependency, improvement in symptoms, and quality of life. For higher-risk patients with MDS, trials should include guidance to prevent dose reductions or delays that could limit efficacy, specify minimal durations of treatment (in the absence of toxicity or progression), and have endpoints focused on overall survival and durable responses. MDS trials should be designed from the outset to allow the practicable application of new therapies in this high-needs population, with drugs that can be administered and tolerated in community settings, and with endpoints that meaningfully improve patients' lives over existing therapies. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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