Hypomethylating Agents Useful in Low-Risk MDS

HOUSTON -- Treatment with hypomethylating agents led to objective responses in a majority of patients with low- and intermediate-risk myelodysplastic syndromes (MDS), according to a study reported here.

Overall, 58 of 113 (53%) patients responded to treatment with low-dose azacytidine or decitabine, including complete responses in a third of cases. Additionally, eight (19%) patients achieved complete cytogenetic responses. Of 56 patients who were transfusion dependent at the start of the trial, 15 (27%) achieved transfusion independence with treatment.

After a median follow-up of 18 months, the median event-free survival (EFS) was 18 months, and median overall survival had yet to be reached. The cohort had a 2-year event-free survival of 39% and 2-year overall survival of 69%. After stratification by International Prognostic Scoring System risk classification, neither EFS nor overall survival had a significant association with disease risk status, Nicholas J. Short, MD, of the University of Texas MD Anderson Cancer Center, and colleagues reported in a poster session at the Society of Hematologic Oncology meeting.

In general, the treatment was well tolerated, as most adverse events were grade 1-2 in severity, the investigators reported. Neutropenic fever occurred in seven (16%) patients. No grade 4 adverse events were reported.

Comorbidity Prominent in MDS Mortality

Almost half of patients with MDS eventually died of the condition or leukemic progression, although a majority patients died of other potentially treatable causes, a review of an NCI database showed.

From 2001 to 2013, 34,904 new diagnoses of MDS were documented in the Surveillance, Epidemiology, and End Results database, and 23,612 (68%) of the patients died. MDS was listed as the cause of 48.4% of the deaths. Second malignancy was listed as cause of death in 4.6% of cases and non-myeloid leukemia in 1.9%, reported Andrew Brunner, MD, of Massachusetts General Hospital in Boston, and co-investigators.

Coronary artery disease (CAD) or stroke accounted for 19.9% of deaths, infection for 5.5%, and chronic obstructive pulmonary disease for 3.5%.

The proportion of attributable deaths varied according to a patient's MDS risk status. The proportion of deaths attributable to MDS increased from 31.5% among low-risk patients to 48.8% in the intermediate-risk category and 74.1% of patients with high-risk MDS. CAD/stroke as the cause of death decreased from a high of 26.3% of patients with low-risk disease to 20.6% of patients with intermediate risk-MDS to 9.3% of patients with high-risk MDS.

Both 12- and 24-month MDS-related mortality increased with MDS risk category. Half of patients with high-risk MDS had died of MDS or myeloid leukemia by 24 months.

"Among MDS patients, death due to MDS or myeloid leukemia is the most common attributed cause of death," the authors concluded. "One year after MDS diagnosis, other causes of death,particularly heart disease, are increasingly common, including among patients with high-risk MDS. Management of comorbid diseases and contribution of MDS to such conditions is important to improve the overall survival of these patients."