In just the last 2 years there have been updates in classification, risk assessment, and response criteria in myelodysplastic syndromes (MDS), but additional efforts are needed to improve these, and there remains a need for better therapies.
New guidelines provide updated classification, prognostication, and response assessment of myelodysplastic syndromes (MDS). These updates were condensed into a report created on behalf of the International Consortium for MDS.
The review is the result of an international workshop held in June 2022 and the findings were published in Blood Reviews. The goal, in addition to summarizing what they learned, was to provide guidance on the updates for physicians in clinical practice.
The purpose of the update was to respond to “significant changes” that had occurred over the last 2 years in MDS. In that time, the World Health Organization (WHO) and the International Consensus Classification (ICC) both published updates. Notably, these had differences in the classification of MDS with ICC creating an “MDS/AML” classification that WHO did not include.
The MDS/AML classification is defined as “10–19% blasts in the peripheral blood and/or bone marrow in the absence of AML-defining genetic abnormalities.” WHO has kept a 20% blasts cutoff to distinguish MDS from AML.
The ICC classification allows patients classified as MDS/AML to be enrolled in either MDS or AML trials and could mean novel therapies approved in AML are used more broadly. WHO’s classification may avoid possible overtreatment of patients with 10% to 19% blasts.
The authors argue for harmonizing the 2 systems. They note that own their own, the 2 classification systems are reasonable, but that “the presence of two parallel and at times conflicting classifications creates confusion for physicians, researchers, regulators and most importantly our patients.”
In addition, in the last 2 years there have also been new prognostic tools that integrate the information on mutations in MDS into scoring systems. Because treatment for MDS can range from simple observation to allogenic stem cell transplantation depending on the disease risk, accurate assessment is crucial in order to match treatment.
These prognostic tools are being used more in clinical decision-making, but it’s unclear how they should be used to guide treatment decisions in practice. The tools available have not been directly compared with one another and were developed using different patients.
The authors also noted that next-generation sequencing (NGS) panels are not widely available in much of the world. “In addition, even in countries in which NGS tools are readily available, their use is not always reimbursed by insurance limiting the access to this technology for some MDS patients,” they wrote.
Finally, the authors reviewed measures of therapeutic success in lower- and higher-risk MDS, shortcomings of those measures, and how updated criteria address those shortcomings.
In approximately 85% of patients with lower-risk MDS, anemia is present at the time of diagnosis, making it the main treatment priority to improve quality of life. Standard of care for these patients is red blood cell transfusions (RBCs), erythropoiesis stimulating agents, and luspatercept and lenalidomide depending on the subtype.
The end points in past clinical trials reflected “modest goals,” the authors wrote. Future trials, they believe, should “be more ambitious” and include end points focused on longer durability of hematologic improvement and RBC transfusion independence. They also wrote that end points measuring disease modification are needed.
Patients with higher-risk MDS have an increased risk of progression to AML, and the goal of treatment in these patients is to alter the course of MDS, delay progression to AML, and prolong survival. Investigational agents are compared with the standard of care for event-based outcome measures such as overall survival (OS), event-free survival (EFS), and progression-free survival.
“However, single arm trials using a variety of different response definitions that seemed promising, have failed to demonstrate in randomized testing EFS or OS benefit for multiple agents,” the authors wrote. “This emphasizes the necessity for well-designed randomized trials so that phase III testing can be rationally prioritized.”
Despite the changes in classifications, risk assessment tools, and response criteria, more work is needed in the future, they wrote. However, what cannot be overlooked is the critical need for research to develop better therapies for patients with MDS.
“Fortunately, multiple agents are in late-stage development for both lower- and higher-risk MDS patients and are poised to change the therapeutic landscape over the next couple of years,” they concluded.
Stahl M, Bewersdorf JP, Xie Z, et al. Classification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): a state-of-the-art report on behalf of the International Consortium for MDS (icMDS). Blood Rev. Published online August 19, 2023. doi:10.1016/j.blre.2023.101128