Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms.

Abstract: Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous, clonal myeloid neoplasms characterized by ineffective hematopoiesis, progressive cytopenias, and an increased risk of progression to acute myeloid leukemia. The diversity in disease severity, morphology, and genetic landscape challenges not only novel drug development but also therapeutic response assessment. The MDS International Working Group (IWG) response criteria were first published in the year 2000 focusing on measures of blast burden reduction and hematologic recovery. Despite revision of the IWG criteria in 2006, correlation between IWG-defined responses and patient-focused outcomes, including long-term benefits, remains limited and has potentially contributed to failures of several phase III clinical trials. Several IWG 2006 criteria also lacked clear definitions leading to problems in practical applications and interobserver and intraobserver consistency of response reporting. Although the 2018 revision addressed lower-risk MDS, the most recent update in 2023 redefined responses for higher-risk MDS and has set out to provide clear definitions to enhance consistency while focusing on clinically meaningful outcomes and patient-centered responses. In this review, we analyze the evolution of the MDS response criteria, limitations, and areas of improvement.
Competing Interests: Conflicts of Interest and Source of Funding: M.S. consulted for Curis Oncology and Boston Consulting; served on the advisory board for Novartis and Kymera; and participated in GME activity for Novartis, Curis Oncology, Haymarket Media, and Clinical Care Options (CCO). A.M.Z. is a Leukemia and Lymphoma Society Scholar in Clinical Research. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Cardiff Oncology, Incyte, Takeda, Novartis, Shattuck Labs, Geron, Aprea, and ADC Therapeutics. A.M.Z. participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Foran, Syros, and Tyme. A.M.Z. served on clinical trial committees for Novartis, Abbvie, Gilead, Syros, BioCryst, Abbvie, ALX Oncology, Geron, and Celgene/BMS. A.M.Z. received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. For the remaining authors, none were declared.
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