Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are a very heterogeneous disease, with extremely variable clinical features and outcomes. Current management relies on risk stratification based on IPSS and IPSS-R, which categorizes patients into low (LR-) and high-risk (HR-) MDS. Therapeutic strategies in LR-MDS pat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4941 |
| _version_ | 1797480068578017280 |
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| author | Giulio Cassanello Raffaella Pasquale Wilma Barcellini Bruno Fattizzo |
| author_facet | Giulio Cassanello Raffaella Pasquale Wilma Barcellini Bruno Fattizzo |
| author_sort | Giulio Cassanello |
| collection | DOAJ |
| description | Myelodysplastic syndromes (MDS) are a very heterogeneous disease, with extremely variable clinical features and outcomes. Current management relies on risk stratification based on IPSS and IPSS-R, which categorizes patients into low (LR-) and high-risk (HR-) MDS. Therapeutic strategies in LR-MDS patients mainly consist of erythropoiesis stimulating agents (ESAs), transfusion support, and luspatercept or lenalidomide for selected patients. Current unmet needs include the limited options available after treatment failure, and the consequent transfusion burden with several hospital admissions and poor quality of life. Therapeutic approaches in HR-MDS patients are aimed at changing the natural course of the disease and hypometylating agents (HMA) are the first choice. The only potentially curative treatment is allogeneic stem cell transplant (allo-HCT), restricted to a minority of young and fit candidates. Patients unfit for or those that relapse after the abovementioned options harbor an adverse prognosis, with limited overall survival and frequent leukemic evolution. Recent advances in genetic mutations and intracellular pathways that are relevant for MDS pathogenesis are improving disease risk stratification and highlighting therapeutic targets addressed by novel agents. Several drugs are under evaluation for LR and HR patients, which differ by their mechanism of action, reported efficacy, and phase of development. This review analyzes the current unmet clinical needs for MDS patients and provides a critical overview of the novel agents under development in this setting. |
| first_indexed | 2024-03-09T21:54:50Z |
| format | Article |
| id | doaj.art-6e6ae68aa087412ab7e9003a79c3cf7a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:54:50Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6e6ae68aa087412ab7e9003a79c3cf7a2023-11-23T19:59:15ZengMDPI AGCancers2072-66942022-10-011419494110.3390/cancers14194941Novel Therapies for Unmet Clinical Needs in Myelodysplastic SyndromesGiulio Cassanello0Raffaella Pasquale1Wilma Barcellini2Bruno Fattizzo3Department of Oncology and Oncohematology, University of Milan, 20122 Milan, ItalyHematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyHematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Oncology and Oncohematology, University of Milan, 20122 Milan, ItalyMyelodysplastic syndromes (MDS) are a very heterogeneous disease, with extremely variable clinical features and outcomes. Current management relies on risk stratification based on IPSS and IPSS-R, which categorizes patients into low (LR-) and high-risk (HR-) MDS. Therapeutic strategies in LR-MDS patients mainly consist of erythropoiesis stimulating agents (ESAs), transfusion support, and luspatercept or lenalidomide for selected patients. Current unmet needs include the limited options available after treatment failure, and the consequent transfusion burden with several hospital admissions and poor quality of life. Therapeutic approaches in HR-MDS patients are aimed at changing the natural course of the disease and hypometylating agents (HMA) are the first choice. The only potentially curative treatment is allogeneic stem cell transplant (allo-HCT), restricted to a minority of young and fit candidates. Patients unfit for or those that relapse after the abovementioned options harbor an adverse prognosis, with limited overall survival and frequent leukemic evolution. Recent advances in genetic mutations and intracellular pathways that are relevant for MDS pathogenesis are improving disease risk stratification and highlighting therapeutic targets addressed by novel agents. Several drugs are under evaluation for LR and HR patients, which differ by their mechanism of action, reported efficacy, and phase of development. This review analyzes the current unmet clinical needs for MDS patients and provides a critical overview of the novel agents under development in this setting.https://www.mdpi.com/2072-6694/14/19/4941myelodysplastic syndromesunmet needstarget therapysomatic mutationsimmunotherapy |
| spellingShingle | Giulio Cassanello Raffaella Pasquale Wilma Barcellini Bruno Fattizzo Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes Cancers myelodysplastic syndromes unmet needs target therapy somatic mutations immunotherapy |
| title | Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes |
| title_full | Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes |
| title_fullStr | Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes |
| title_full_unstemmed | Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes |
| title_short | Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes |
| title_sort | novel therapies for unmet clinical needs in myelodysplastic syndromes |
| topic | myelodysplastic syndromes unmet needs target therapy somatic mutations immunotherapy |
| url | https://www.mdpi.com/2072-6694/14/19/4941 |
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