ASCO 2011: Better Knowledge, Better Treatments in Myelodysplatic Syndromes

A growing understanding of the biology behind myelodysplastic syndromes (MDS) is leading the way to improved treatment options, according to two presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Bone marrow smear from a patient with RAEB and an isolated 5q-chromosome abnormality showing two small megakaryocytes with nonlobulated nuclei. The cytoplasm is well granulated.

"For years, we've made treatment decisions based purely on clinical features. But now we're seeing a change," said Alan List, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., speaking at a session on Monday.

The clonal stem cell disorder affects approximately 4 of every 100,000 people annually, with about a third of patients progressing to acute myeloid leukemia.

Over the last several years, scientists have recognized that the biology of MDS is characterized by increased apoptosis, or programmed cell death, as well as a range of cytogenetic, epigenetic, molecular and immune abnormalities, noted Pierre Fenaux, MD, PhD, of Hopital Avicenne in Bobigny, France.

An interstitial 5q deletion, for example, is now known to be the most common chromosomal anomaly in the disorder. Meanwhile, many gene mutations such as TET2 and JAK2 have been linked, with more than half of MDS patients carrying at least one identified mutation.

Researchers have also found that aberrant DNA methylation is a dominant mechanism in the progression of MDS to acute myeloid leukemia.

The advent of SNP array technology is responsible for much of this increased understanding and the resulting development of sophisticated prognostic tools, which go beyond classical factors such as the percentage of myeloblasts in the bone marrow.

"It's been a breakthrough in MDS," said Dr. Fenaux.

These advances have also opened the door to a range of hopeful new therapeutic strategies.

Recent research suggests that presence of a TET2 mutation predicts a favorable response to treatment with azacitidine. Dr. List noted that lenalidomide appears similarly beneficial for patients carrying a 5q deletion, with about a third reaching transfusion independence compared to about a quarter of those without the mutation.

Further, patients with evidence of autoimmune involvement such as T-cell proliferation may fare well with antithymocyte globulin and cyclosporine, and those with a score of 2 based on flow cytometry and serum erythropoietin levels will likely do well on an erthropoiesis-stimulating agent.

"We can make a treatment selection based on what the biology is telling us," noted Dr. List.

"But it's important to note that we're not treating acute myeloid leukemia," he added. "So we don't need to achieve complete response for patients to extend survival. Long-term treatment is key."

Just as basic science is improving researchers' ability to identify novel treatments, better therapies are putting the pressure back on biologists.

"With the advance of new treatments, we need to identify more prognostic factors," noted Dr. Fenaux. "We still don't know enough."