New Criteria and Novel Agents May Help Spur MDS Advances

Published: Saturday, Jun 18, 2016
Mikkael A. Sekeres, MD, MS

Mikkael A. Sekeres, MD, MS

Although knowledge about the underlying biology of myelodysplastic syndromes (MDS) has expanded rapidly in recent years, translating those findings into advances in the diagnosis and management of patients remains a significant challenge. Key research is focused on the development of drugs for lower-risk patients and second-line therapies for high-risk individuals.

That was the picture that emerged from a panel of experts who discussed key issues in MDS during a recent OncLive Peer Exchange® roundtable entitled “Myelodysplastic Syndromes: Translating Genetics to Clinical Practice.”

“We’re in a remarkable time in the study of MDS where our understanding of the biology is skyrocketing, and we can only hope that the therapies we have available to treat our patients are going to catch up soon,” said Mikkael A. Sekeres, MD, MS, who served as moderator for the discussion.

 
Ellen K. Ritchie, MD

Ellen K. Ritchie, MD

Panelist Ellen K. Ritchie, MD, believes that an increased interest in aging is coinciding with efforts to develop strategies for MDS. “We’re finding that there are mutations that occur as people age that may have dovetailed into the development of disease,” she said. “There is a potential that we could interfere in the early phase of patients who are developing MDS. I think that this is a really exciting avenue of study and we really look forward to seeing what happens in the next few years.”

Defining and Diagnosing MDS

MDS represent a heterogeneous spectrum of hematopoietic disorders, with allogeneic stem cell transplantation being the only curative option currently available, Sekeres noted. Most patients have an acquired somatic gene mutation in the clone, with the hallmark of the clone being ineffective hematopoiesis, said Rami S. Komrokji, MD. Yet, this is not to minimize the role of the microenvironment, he said. “In addition to the clone of the acquired somatic mutations, we have immune response, we have an inflammation going in the microenvironment that definitely contributes probably early on in the disease and to the myelosuppression observed,” Komrokji said.

 
Rami S. Komrokji, MD

Rami S. Komrokji, MD

Komrokji also acknowledged that “in a subset of patients we cannot identify clonal events,” either because of limitations of current technology or because these patients might not truly have MDS.

Indeed, panel member Jamile M. Shammo, MD, objected to labeling all cases of MDS as a malignancy. “I tend to think that perhaps on one end of the spectrum, there’s certainly clones and malignancies and propensity for AML [acute myeloid leukemia] development, but on the other side is merely manifestation of bone marrow failure without necessarily having any clones,” Shammo said.

The conundrum extends to how physicians discuss MDS with their patients. Ritchie believes it is important to talk about the spectrum of the disease and not “label it with the big C, necessarily,” because of the detrimental impact that such a characterization can have on the patient’s quality of life. Yet, as Komrokji said, a cancer diagnosis may help patients secure insurance coverage. Further, Sekeres said that the patient who thinks the illness is just a mild blood disorder may be resistant to tolerating the challenges accompanying chemotherapy, thus endangering long-term survival.

The World Health Organization (WHO) is in the process of revising its classification system for MDS, which is currently based on clinical features, peripheral blood and bone marrow findings, and cytogenetic analysis.1 Shammo said the new version may be more streamlined so that it is easier to classify patients and study MDS prospectively. However, Komrokji does not expect the revised WHO system to integrate acquired somatic mutations into the diagnostic criteria.


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