Please verify you are a healthcare professional

The information contained in this site is intended for healthcare professionals only.
Yes, I am a healthcare professional and would like to continue.

Disease overview

MDS is a group of clonal hematologic malignancies that occur when the blood-forming cells in the bone marrow become dysplastic (or abnormal) and have abnormal cellular development.1

This dysplasia is caused by abnormal hematopoietic stem cell differentiation and maturation, as well as a significant increase in cell death in the bone marrow.2

Signs and symptoms of MDS usually include anemia, fatigue, shortness of breath, infections due to neutropenia, and bruising from thrombocytopenia. These signs and symptoms, when coupled with the comorbidities often seen in this primarily 65+ year old patient population, can severely impact quality of life and further complicate treatment.3-9

Therapies

Current and future therapies aim to restore normal hematopoiesis so that the body can produce the healthy cells required to fight back against disease10-12

Patients diagnosed with HR-MDS have a poor prognosis7

<ul> <li>Approximately forty percent of patients with MDS are diagnosed as higher risk<sup>13</sup></li> </ul>
Median survival in MDS per IPSS-R risk group13
Very low 8.8 years Diagnosed with LR-MDS
Low 5.3 years
Intermediate 3.0 years Diagnosed with HR-MDS
High 1.6 years
Very high 0.8 years

More than half of patients with HR-MDS progress to AML3

The evolving prognostic scoring system in MDS

MDS exists along a continuous disease spectrum, with subtypes primarily categorized based on these 5 factors per the IPSS‑R5,13:

  1. The percentage of blasts in the bone marrow
  2. The type and number of chromosomal abnormalities in the cells
  3. Hemoglobin levels
  4. Platelet levels
  5. Neutrophil levels

Each of the above factors is given a risk score that coincides with the relevant ranges for each prognostic variable.

The IPSS-R, which was released in 2012 by the International Working Group for Prognosis in MDS (IWG-PM), is still the most widely used scoring system in MDS. Stratification of patients at diagnosis is based on blood counts, morphology, and cytogenetic abnormalities.4,14

To improve the risk stratification of patients with MDS, the IWG-PM released the IPSS-M in 2022, which uses a combination of genomic profiling, hematologic parameters, and cytogenetic abnormalities. This new scoring system categorizes patients with LR-MDS as very low, low, and moderate low, and patients with HR-MDS as moderate high, high, and very high. The goal of these new guidelines is to improve risk stratification and better inform treatment decisions by considering the results of genomic testing.14

AML, acute myeloid leukemia; HR-MDS, higher-risk myelodysplastic syndrom; IPSS-M, Molecular International Prognostic Scoring System; IPSS-R, Revised International Prognostic Scoring System; LR-MDS, lower-risk myelodysplastic syndrome; MDS, myelodysplastic syndrome.

References: 1. Dao KT. Myelodysplastic syndromes: updates and nuances. Med Clin N Am. 2017:333-350. 2. Menssen AJ, Walter MJ. Genetics of progression from MDS to secondary leukemia. Blood. 2020;136(1):50-60. 3. Signs and Symptoms of Myelodysplastic Syndromes. American Cancer Society. January 22, 2018. Accessed March 3, 2023. https://www.cancer.org/content/dam/CRC/PDF/Public/8745.00.pdf. 4. Platzbecker U, Kubasch AS. Current challenges and unmet medical needs in myelodysplastic syndromes. Leukemia. 2021;35:2182-2198. 5. Benton CB, Khan M, et al. Prognosis of patients with intermediate risk IPSS-R myelodysplastic syndrome indicates variable outcomes and need for models beyond IPSS-R. Am J Hematol. 2018;93:1245-1253. 6. Garcia-Manero G, Chien KS, et al. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2020;95:1399-1420. 7. Sanz GF. In MDS, is higher risk higher reward? Hematology. 2019;381-390. 8. Mohty R, Hamed RA, et al. Treatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher‑risk disease. Journal of Hematology & Oncology. 2022;15(124):1-16. 9. Rozema J, Hoogendoorn M, et al. Comorbidities and malignancies negatively affect survival in myelodysplastic syndromes: a population-based study. Blood Advances. 2021;5(5)1344-1351. 10. Issa JJ, Roboz G, et al. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol. 2015:1-12. 11. Garcia-Manero G, Fenaux P, et al. Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial. Lancet Oncol. 2016;17(4):496-508. 12. Tamibarotene Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome (recruiting). NCT04797780. February 27, 2023. Accessed March 3, 2023. https://clinicaltrials.gov/ct2/show/NCT04797780. 13. Greenberg PL, Tuechler H, et al. Revised International Prognostic Scoring System for Myelodysplastic Syndromes. Blood. 2012;120(12):2454-2465. 14. Bernard E, Tuechler H, et al. Molecular International Prognostic Scoring System for myelodysplastic syndromes. NEJM Evid. 2022;1(7):1-14.

Current treatment landscape1,2

The only approved first-line therapies for HR-MDS are HMAs, such as azacitidine, decitabine, or decitabine/cedazuridine1,2

However, only 30% of patients with HR-MDS achieve either a complete remission or partial remission with HMAs, and there are no FDA-approved targeted therapies for patients who are HMA refractory.3,4

The only potentially curative approach for this patient group is an allogeneic HSCT, which is limited to a small number of eligible patients.1

Several factors make disease management challenging1,2,4-6:

  • The advanced age of the patient (65+)
  • Associated comorbidities, such as diabetes, cardiovascular disease, and chronic pulmonary disease
  • Limited treatment options
  • The complexity and diversity of the genetic abnormalities that drive disease

There remains a significant unmet need for patients with HR-MDS2,6

Current treatments offer low remission rates, poor quality of life, and limited overall survival. Recent advances have helped improve our understanding of the complex pathogenesis of MDS and identify promising new biomarkers and therapeutic targets—including targets for cellular differentiation.

HMA, hypomethylating agent; HR-MDS, higher-risk myelodysplastic syndrome; HSCT, hematopoietic stem cell transplantation.

References: 1. Sanz GF. In MDS, is higher risk higher reward? Hematology. 2019;381-390. 2. Mohty R, Hamed RA, et al. Treatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher‑risk disease. Journal of Hematology & Oncology. 2022;15(124):1-16. 3. Fenaux P, Mufti GJ, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223-232. 4. Bewersdorf JP, Carraway H. Emerging treatment options for patients with high-risk myelodysplastic syndrome. Ther Adv Hematol. 2020;11:1-22. 5. Rozema J, Hoogendoorn M, et al. Comorbidities and malignancies negatively affect survival in myelodysplastic syndromes: a population-based study. Blood Advances. 2021;5(5)1344-1351. 6. Platzbecker U, Kubasch AS. Current challenges and unmet medical needs in myelodysplastic syndromes. Leukemia. 2021;35:2182-2198.