TY - JOUR
T1 - Current status of phase 3 clinical trials in high-risk myelodysplastic syndromes
T2 - pitfalls and recommendations
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/1
Y1 - 2023/1
N2 - Single-agent hypomethylating agents remain the cornerstone of treatment for patients with high-risk myelodysplastic syndromes. Although these agents have clinical activity and can improve the overall survival of these patients, their impact on the natural history of myelodysplastic syndromes is only partial. Therefore, we need either newer agents or combinations that could have a greater impact on the survival of our patients. Over the past decade there has been an increased effort in drug development for myelodysplastic syndromes. Hypomethylating agent combinations that have been explored over the past decade include agents that block mutant TP53, NEDD inhibitors, BCL-2 inhibitors, and antibodies such as sabatolimab or magrolimab. Despite initial encouraging results, two registration trials from 2021 and 2022 have not been successful in improving outcomes when compared with single-agent hypomethylating agents. Here, I summarise the current status of ongoing phase 3 trials for patients with untreated high-risk myelodysplastic syndromes and provide some suggestions for future designs.
AB - Single-agent hypomethylating agents remain the cornerstone of treatment for patients with high-risk myelodysplastic syndromes. Although these agents have clinical activity and can improve the overall survival of these patients, their impact on the natural history of myelodysplastic syndromes is only partial. Therefore, we need either newer agents or combinations that could have a greater impact on the survival of our patients. Over the past decade there has been an increased effort in drug development for myelodysplastic syndromes. Hypomethylating agent combinations that have been explored over the past decade include agents that block mutant TP53, NEDD inhibitors, BCL-2 inhibitors, and antibodies such as sabatolimab or magrolimab. Despite initial encouraging results, two registration trials from 2021 and 2022 have not been successful in improving outcomes when compared with single-agent hypomethylating agents. Here, I summarise the current status of ongoing phase 3 trials for patients with untreated high-risk myelodysplastic syndromes and provide some suggestions for future designs.
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U2 - 10.1016/S2352-3026(22)00265-4
DO - 10.1016/S2352-3026(22)00265-4
M3 - Review article
C2 - 36215988
AN - SCOPUS:85144635657
SN - 2352-3026
VL - 10
SP - e71-e78
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 1
ER -