SY-1425 + Azacitidine for Myelodysplastic Syndromes

The average age of diagnosis of myelodysplastic syndrome in the USA is 67.0 years for males and 58.8 years for females. The yearly incidence is 22 new cases per 100,000 inhabitants aged 18 years with a mean duration that is 7.7 years ago of diagnosis of myelodysplastic syndrome. The most frequent clinical sub-types are: chronic myeloid leukemia (7.5% of new cases), monoclonal gammopathy of undetermined significance (2.4%) and refractory anemia, chronic (1.1%).

The overall 5-year survival of patients with MDS is 63%, but when a complete remission of myelodysplasia can be reached, the 5-year overall survival is up to 95%.

MDS involves impaired blood cell production that can progress to MDS Type I and Type II. MDS-I is a specific disease involving defects in the marrow. It can progress to leukaemia. Patients with MDS Type III disease can suffer from other types of cancer. Patients should be monitored for changes in the marrow that can potentially lead to worsening symptoms.

Inherited mutations in cell cycle regulators, such as TP53 can cause myelodysplastic syndromes. Genetic variation in the 5-aminosalicylate biosynthetic pathway lead to increased production of AMP by MDS-derived precursors and subsequent oncogenic effects.

Signs of myelodysplastic syndromes will evolve over time; therefore, an individual must be aware of their signs. For example, they may not have as much blood in their stool as expected (anemia) or they may find it hard to urinate (dysuria).

Most patients with MDS receive thalidomide as a part of their disease. A larger percentage of patients with a good response receive cladribine. Other agents used include alkylating drugs, azacitidine, and cytarabine. Patients with good quality of life can often be treated with supportive care to prolong survival.

Sy-1425 + TAC regimen can significantly improve the D-PANSS and QOL for patients with myelodysplastic syndromes compared with the TAC regimen alone. Findings from a recent study are consistent with those from other trials in myelodysplastic syndromes and pave the way forward for future trials to investigate the role of adjuvant azacitidine combined with other novel agents for myelodysplastic syndromes.

Although certain mutations have been identified in MDS, their prevalence in this disorder is small. The pathologic mechanism(s) of the disorder are still unknown. The clinical presentation and response to therapy of MDS vary greatly among individuals.

Although the most effective agents are still under investigation, some of the drugs already approved for other indications have been found to be active for improving the quality of life in patients with MDS.

Data from a recent study demonstrate that sy-1425 is efficacious in altering the epigenome and warranting further investigations into how sy-1425 + azacitidine might be used as a treatment for myelodysplastic syndromes (MDS).

The average survival rate of myelodysplastic syndromes is approximately 3 years. Patients who are in the MDS phase of life typically have the longer survival rate than patients who are older. This is because patients who are older are likely to have other health problems that affect their quality of life. However, patients who are in the MDS phase are more likely to be overweight as well as have a white blood cell count >2 x 10 but less than 10 x 10/uL in which case a bone marrow biopsy may be conducted. However, the bone marrow biopsy has an 85% sensitivity and 92% specificity for distinguishing among different types of MDS and detecting progression towards acute myeloid leukemia.