Early, Attenuated-Dose Hypomethylating Agent Therapy May Be Effective in Low-Risk MDS

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The impact of this attenuated-dose hypomethylating agents among patients with low-risk myelodysplastic syndrome who are transfusion independent requires further investigation.
The impact of this attenuated-dose hypomethylating agents among patients with low-risk myelodysplastic syndrome who are transfusion independent requires further investigation.
The following article features coverage from the American Society of Clinical Oncology (ASCO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

Attenuated doses of hypomethylating agents (HMA) early in treatment could improve outcomes among transfusion independent patients with lower-risk myelodysplastic syndromes (MDS), according to findings that will be presented at the American Society of Clinical Oncology 2018 Annual Meeting in Chicago, Illinois.1

HMAs are the standard of care among patients with higher-risk MDS, but the affect of this treatment among patients with lower-risk MDS that are transfusion independent requires further investigation.

In this study, researchers assessed the outcomes of 87 patients with low- or intermediate-1-risk MDS who were treated with attenuated doses of HMAs between 2012 and 2017. Study patients received intravenous (IV) decitabine 20 mg/m2 or azacitidine 75 mg/m2. Study participants were all transfusion independent at the start of the study.

According to the International Prognostic Scoring System (IPSS) 66% (57) and 34% (30) of patients were intermediate-1- and low-risk, respectively, and 59% (51), 26% (23) and 15% (13) were considered intermediate, high, and low risk, respectively by the MD Anderson Cancer Center Lower Risk Prognostic Model. Seven percent (6), 25% (22), and 68% (59) of patients had poor, intermediate, and good cytogenetics, respectively.

Of 80 evaluable patients, the overall response rate was 74% including a complete response rate of 50%. The median overall survival was not evaluable at the time of analysis, and the median event-free survival was 35.4 months.

Three percent (2) of patients had progressive disease, 24% (19) did not respond to treatment, 8% (6) progressed to acute myeloid leukemia; at the time of response analysis, 6% (5) became transfusion dependent.

TET2 mutations occurred in 30%, ASXL1 mutations occurred in 9%, and RUNX1 mutations occurred in 8% of study patients.

The authors concluded that “early intervention with attenuated doses of HMAs in [transfusion independent patients] with lower risk MDS is safe and active and could potentially alter the natural history of MDS.”

Read more of Cancer Therapy Advisor's coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

  1. 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. Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.

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