Potential steps to achieve MDS priority research goals
| Priority research goals . | Action steps . |
|---|---|
| 1 | - Development of new frontline treatment of MDS: Several large, randomized trials, including azacitidine in combination with the BCL-2 inhibitor venetoclax, the anti CD47 antibody magrolimab and the anti TIM3 antibody sabatolimab are ongoing |
| 2 | - Development of treatment options for DNMTi-refractory MDS: Several early phase clinical trials are ongoing; however, no therapy is approved yet at time of DNMTi resistance |
| 3 | - Develop trials with broad inclusion of both TP53 mutated MDS and AML - Focus on trials with emphasis on engaging the immune system instead of chemotherapy based clinical trials - Utilize platform-based approaches to conduct multiple randomized phase II trials to establish a promising approach for phase III testing early (eg, NCI myeloMATCH) |
| 4 | - Palliative goals of treatment in LR-MDS are somewhat antithetical, considering that for patients with CH, a primary effort is to prevent the progression of disease. The focus of drug development should be on reversing the underlying pathophysiology of the disease. - One promising area of investigation is targeting immune dysregulation in MDS clones and the BM microenvironment (eg, targeting IRAK1/4 and/or the NLRP3 inflammasome) |
| 5 | - Expand eligibility to be representative and inclusive of the population including minority and underserved populations - Partner with pharmaceutical companies, government and regulatory agencies with a shared mission and set of goals - Inclusion of HRQoL and other type of PROs should always be considered for phase III trials to generate definite data that can facilitate clinical-decisions |
| 6 | - Formulate one single set of consensus diagnostic criteria (WHO classification has historically represented the gold standard in pathological classification) |
| 7 | - Update the International Working Group 2006 response criteria for higher-risk MDS with emphasis on association with long term benefit - Systematically and prospectively validate specific blood count cut-offs in response criteria - Eliminate response criteria without clear association with improvement in overall survival (eg, mCR without hematologic improvement) |
| 8 | - Secondary prevention of progression from CHIP to MDS in germ line predisposed, those receiving cytotoxic exposures, or acquired with age are all components of the same broader goal. - Develop practical decision-making tools to guide hematologists, medical oncologists, and patients alike in balancing the risks and benefit of adjuvant chemotherapy and radiation therapy in patients with high-risk CH |
| 9 | - Develop strategies to allow data sharing between large registries in the U.S. (National MDS Natural History Study and the Connect Myeloid Disease registry) and Europe (HARMONY Alliance and the MDS-RIGHT project) - Accomplishing these goals will require to overcome several bureaucratic and regulatory hurdles and necessitates sensitivity to the distinct privacy laws in Europe and the U.S. |
| 10 | - Utilize and widely distribute the improved in vivo modeling systems for MDS preclinical studies (eg, “MISTRG” mice) |
| Priority research goals . | Action steps . |
|---|---|
| 1 | - Development of new frontline treatment of MDS: Several large, randomized trials, including azacitidine in combination with the BCL-2 inhibitor venetoclax, the anti CD47 antibody magrolimab and the anti TIM3 antibody sabatolimab are ongoing |
| 2 | - Development of treatment options for DNMTi-refractory MDS: Several early phase clinical trials are ongoing; however, no therapy is approved yet at time of DNMTi resistance |
| 3 | - Develop trials with broad inclusion of both TP53 mutated MDS and AML - Focus on trials with emphasis on engaging the immune system instead of chemotherapy based clinical trials - Utilize platform-based approaches to conduct multiple randomized phase II trials to establish a promising approach for phase III testing early (eg, NCI myeloMATCH) |
| 4 | - Palliative goals of treatment in LR-MDS are somewhat antithetical, considering that for patients with CH, a primary effort is to prevent the progression of disease. The focus of drug development should be on reversing the underlying pathophysiology of the disease. - One promising area of investigation is targeting immune dysregulation in MDS clones and the BM microenvironment (eg, targeting IRAK1/4 and/or the NLRP3 inflammasome) |
| 5 | - Expand eligibility to be representative and inclusive of the population including minority and underserved populations - Partner with pharmaceutical companies, government and regulatory agencies with a shared mission and set of goals - Inclusion of HRQoL and other type of PROs should always be considered for phase III trials to generate definite data that can facilitate clinical-decisions |
| 6 | - Formulate one single set of consensus diagnostic criteria (WHO classification has historically represented the gold standard in pathological classification) |
| 7 | - Update the International Working Group 2006 response criteria for higher-risk MDS with emphasis on association with long term benefit - Systematically and prospectively validate specific blood count cut-offs in response criteria - Eliminate response criteria without clear association with improvement in overall survival (eg, mCR without hematologic improvement) |
| 8 | - Secondary prevention of progression from CHIP to MDS in germ line predisposed, those receiving cytotoxic exposures, or acquired with age are all components of the same broader goal. - Develop practical decision-making tools to guide hematologists, medical oncologists, and patients alike in balancing the risks and benefit of adjuvant chemotherapy and radiation therapy in patients with high-risk CH |
| 9 | - Develop strategies to allow data sharing between large registries in the U.S. (National MDS Natural History Study and the Connect Myeloid Disease registry) and Europe (HARMONY Alliance and the MDS-RIGHT project) - Accomplishing these goals will require to overcome several bureaucratic and regulatory hurdles and necessitates sensitivity to the distinct privacy laws in Europe and the U.S. |
| 10 | - Utilize and widely distribute the improved in vivo modeling systems for MDS preclinical studies (eg, “MISTRG” mice) |