Myelodysplastic syndrome (MDS) cases are rising with an aging demographic. Although treatments have come a long way, novel therapies are still needed to improve outcomes. A recent review article published in Cancers summarized the current understanding of MDS, existing therapeutics, and what’s on the horizon.
Next-generation sequencing (NGS) has expanded the understanding of MDS, but developing precision medicine for genetic targets remains a challenge. Younger, fit patients with MDS may have curative treatment with allogeneic hematopoietic stem cell transplantation (aHSCT). However, ineligible patients have palliative therapy and eventually progress in their disease.
Basics of MDS
MDS mostly affects older patients, with a median age at presentation of more than 70 years. NGS has helped understand the genetics of MDS, but the molecular mechanisms involved in disease progression are not fully understood, making it difficult to develop targeted therapies.
The heterogeneity of MDS presents challenges to treatment. Patients with lower-risk MDS have a median survival of 3 to 8 years, and patients with high-risk MDS have a median survival of 1 to 3 years.
Currently Available MDS Therapies
Patients with lower-risk MDS and asymptomatic cytopenia may undergo watchful waiting, whereas patients with symptomatic anemia may undergo red blood cell transfusions and/or therapy with erythropoietin-stimulating agents (ESAs).
Some patients with lower-risk MDS with del(5q) may be eligible for disease-modifying therapy with lenalidomide. Other lower-risk and higher-risk patients may benefit from hypomethylating agents (HMAs).
Younger, fit patients can undergo induction chemotherapy followed by aHSCT. This remains the only curative option for higher-risk MDS in fit patients younger than 75 years.
Ongoing Clinical Trials
LUSPA is being investigated a first-line therapy for lower-risk MDS in a phase 3, placebo-controlled clinical trial that includes patients with transfusion-dependent MDS.
An oral spliceosome modulator is being evaluated in preclinical trials for patients with higher-risk MDS. Other HMAs are also in development for this patient population and HMAs combined with immune checkpoint inhibitors (ICIs).
The study authors developed a set of 29 guideline-based indicators to measure quality of care based on diagnosis, treatment, and provider/infrastructure characteristics. The goal of the indicators is to provide more structure and systematic assessment of MDS.
Ongoing research continues to focus on understanding the pathogenesis of disease to develop novel precision medicine therapies, as well as to develop more systematic approaches to diagnosis and care.
Chanias I, Stojkov K, Stehle GT, et al. Myelodysplastic syndromes in the postgenomic era and future perspectives for precision medicine. Cancers (Basel). 2021;13(13):3296. doi:10.3390/cancers13133296