Poor Prognosis After Transformation to AML Following HMA Therapy in MDS

HOUSTON — Clinical outcomes are “extremely poor” in patients with myelodysplastic syndromes (MDS) after failure with hypomethylating agent (HMA) therapy and whose disease has transformed into acute myeloid leukemia (AML), according to a recent study.

“The outcomes of AML transformation after HMA-failure MDS remain extremely poor,” the investigators, led by Kunwha Kim, MD, MPH, of the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston, wrote.

The goals of the study, which was presented at the 10th Annual Meeting of the Society of Hematologic Oncology, were to understand the clinical characteristics and outcomes of AML transformation after HMA failure in MDS.

The retrospective study analyzed 147 patients with newly diagnosed MDS from 2017 to 2021 who later developed HMA failure, with a focus on AML transformation in these patients. The median follow-up was 19.5 months, and 71% of the patients developed AML after failure with HMA therapy.

The investigators noted the patients with AML transformation were “likely to be younger, have higher bone marrow or peripheral blasts, and lower platelet counts at the time of MDS diagnosis.” Other clinical characteristics included higher-risk MDS per the Revised International Prognostic Scoring System, more adverse cytogenetics, and more frequent TP53 mutations and less frequent SF3B1 mutations at MDS diagnosis.

Patients with AML transformation had a shorter time from diagnosis to HMA failure (7.5 versus 15 months; P<.001). Once HMA failure occurred, patients with AML transformation had lower overall survival (OS; 4.2 vs 8.4 months; P=.003). In patients with AML transformation, the median OS after AML diagnosis was four months.

After transformation, the patient prognosis was poor, with no association between survival and the type or intensity of treatment. Most patients died of refractory disease (73%) or complications from pancytopenia (19%), with 60- and 180-day mortality rates of 33% and 69%, respectively. Therapy-related disease, European LeukemiaNet adverse risk, higher risk cytogenetics, and TP53 and KRAS mutations were associated with worse survival.

“Further understanding of the biology and disease characteristics of this patient population is warranted for better treatment approaches,” Dr. Kim and colleagues concluded.

Reference

Kim K, Ong F, Li Z, et al. Outcomes of transformation to acute myeloid leukemia after hypomethylating agent therapy in patients with myelodysplastic syndromes. Abstract # MDS-431. Presented at the 10th Annual Meeting of the Society of Hematologic Oncology, September 28-October 1, 2022.