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Low-dose hypomethylating agents (HMAs) was associated with favorable outcomes in previously untreated lower-risk myelodysplastic syndromes (MDS), according to a long-term analysis of a .

With a follow-up of 68 months, median event-free survival and overall survival were 17 months and 33 months, respectively, with two low-dose HMAs, reported Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.

Among the 113 patients in the study, the overall response rate was 67% in those who received low-dose decitabine versus 48% in those who received low-dose azacitidine (P=0.042), with 36% and 35% achieving complete responses.

Of the 59 patients who were transfusion dependent before starting therapy, 41% of the decitabine patients and 15% of the azacitidine patients achieved transfusion independence (P=0.039), with a median duration of independence of 22 months, they noted in .

"Approximately half of the patients maintained their responses over 1 year, one quarter over 2 years, and 10% of patients over 4 years," the authors wrote. "Given that the cause of death in 84% of patients with lower-risk MDS was MDS-related deaths, including infection, transformation to acute myeloid leukemia (AML) and hemorrhage, the determination of complete response in patients with lower-risk MDS may prevent complications from cytopenia and potentially MDS-related deaths."

Patients with MDS are, in general, divided into lower- versus higher-risk categories based on bone marrow blast percentage, karyotype, and cytopenias, and most patients with higher-risk MDS are treated with HMAs.

"In contrast, the role of the HMAs in lower-risk MDS is less well understood and not globally accepted," Garcia-Manero and colleagues explained. "The aims of this study are to better understand the impact of attenuated HMA dosing in lower-risk MDS."

For this analysis, Garcia-Manero and team enrolled 113 patients (median age 70) with previously untreated MDS from November 2012 to February 2016; 73 were treated with decitabine 20 mg/m² IV daily and 40 were treated with azacitidine 75 mg/m² IV or subcutaneously daily on days 1 to 3 every 28-day cycle.

Patients were eligible if they had an Eastern Cooperative Oncology Group performance status of 0 to 2, had not received prior HMA treatment, and had a blood total bilirubin <2 mg/dL and a serum creatinine <2 mg/dL. Patients who had received other prior treatments for MDS, including growth factors, were eligible.

Twenty-two patients had low-risk MDS and 91 had intermediate-1-risk MDS by the International Prognostic Scoring System (IPSS).

The authors used an adaptive randomization scheme in assigning patients to the two treatment arms based on response rate after the second cycle of therapy. As a result, due to the to the higher rate of response among the first 20 patients enrolled, more patients were assigned to the decitabine group.

Thirteen patients had transformation to AML, with a median time to transformation of 11 months (range 4.0 to 38.7 months). Of these patients, two had lower risk by the revised IPSS, seven had intermediate risk, and four had high risk.

According to the IPSS, median overall survival was not reached, 34 months, and 28 months in the low-, intermediate-, and high-risk groups, respectively, while 5-year overall survival rates were 52%, 38%, and 22%, respectively.

Dose reductions were allowed for patients with grade 3/4 toxicities. Responding patients were allowed to continue treatment indefinitely.

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