Highlight from ASCO 2018: Attenuated Doses of HMAs in Low-risk MDS

Clinical Commentaries published on July 23, 2018
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Eunice S. Wang, MD
Chief, Clinical Leukemia Service
Professor, Department of Medicine
Roswell Park Comprehensive Cancer Center
Buffalo, New York

Highlight from ASCO 2018: Attenuated Doses of HMAs in Low-risk MDS

This is an abstract involving the treatment of lower-risk MDS patients. The standard of care for higher-risk MDS patients is really azacitidine or decitabine. Azacitidine at least has been shown to result in overall survival benefit in these individuals, and it is really considered the agent that most of us would start with on those higher-risk patients with poor cytogenetics and prolonged cytopenia.

What Dr. Swaminathan and colleagues demonstrated in this study from MD Anderson is that there may be a role for hypomethylating agents in lower-risk MDS. Lower-risk MDS patients (typically untreated) have an overall survival of anywhere between three and a half to six years. Generally, per NCCN national guidelines, we do not treat these individuals until they develop transfusion dependence, or if they start to look like they are going to transform to AML with increased marrow blasts. This was a retrospective study that looked at 80 patients treated at MD Anderson with very short courses of hypomethylating agents: decitabine for three days or azacytidine for three to five days. These patients were not transfusion-dependent and received multiple cycles of therapy without significant hematologic toxicity. There were actually no deaths on the study, it was very well-tolerated. Overall response rates were also pretty impressive: 74% in this patient population. The authors here and in another publication have stated that there is a potential for this attenuated hypomethylating course to really alter the natural history of this lower risk-disease. That would be a big change because for now, we do not really treat these individuals until they get sicker. To start these agents earlier would be a little bit of paradigm shift. There are some limitations with the study. This was a retrospective analysis of data that they collected on 80 patients in a single institute. They used a couple of different chemotherapy regimens and they used a heterogeneous population; about three-quarters of the patients had intermediate risk disease.

There is currently a phase 3 trial looking at the same patient population with the same regimen. We are going to have to wait for that data before we can truly say that this is an advance. The thing that I am worried about is the median overall survival for these patients has not been reached. Is this really going to be an advance, or maybe these patients would have just done fine with even no treatment, or any kind of treatment. I think it is really hard to know and given the prolonged survival, I think we are going to need to wait a little bit longer to see if that is going to change the standard of care.

Reference

Swaminathan M, Jabbour E, Ravandi F, et al. Association of early intervention in transfusion independent (TI) patients (Pts) with lower-risk myelodysplastic syndromes (MDS) treated with attenuated doses of hypomethylating agents (HMAs) with high response rates and long duration of response. ASCO 2018. Abstract 7001.
https://meetinglibrary.asco.org/record/161754/abstract

Last modified: July 18, 2018