Proposed Updates to Treatment Response Criteria for Patients With Myelodysplastic Syndromes
The current set of standardized treatment response criteria was most recently revised in 2006 and had many shortcomings when applied to clinical trials.
In an article published in Blood, an International Working Group (IWG) proposed new revisions to a previously published set of standardized treatment response criteria for patients with myelodysplastic syndromes (MDS), which were last revised in 2006.
The IWG was composed of a panel of MDS experts from countries in the European Union and North America. The proposed revisions focused primarily on better defining the treatment response criteria for hematologic improvement in patients with MDS, particularly for erythroid response evaluation.
Transfusion dependence in patients receiving red blood cell (RBC) transfusions is currently defined as having hemoglobin level (Hb) below 9 g/dL and receiving 4 or more units of RBCs within 8 weeks. The IWG suggested that this definition did not adequately define a prescreening period and failed to account for patients receiving fewer than 4 units of RBCs. They recommended instating a prescreening period of 16 weeks and categorizing patients as nontransfused, low transfusion burden (receiving 3-7 units of RBCs within 16 weeks), and high transfusion burden (receiving ≥ 8 units of RBCs within 16 weeks).
To determine baseline Hb, the IWG proposed taking Hb measurements biweekly during the 16 week prescreening period and calculating the mean of these measurements. Furthermore, they suggested changing the threshold for treatment initiation from baseline Hb less than 11 g/dL to Hb less than 10 g/dL.
An erythroid response evaluation period of 16 weeks, beginning from week 0 of treatment initiation, was recommended. During this period, erythroid response in nontransfused patients was defined as achieving 2 consecutive measurements of Hb greater than 1.5 g/dL, and response in high or low transfusion burden patients was defined as achieving transfusion independence.
To avoid bias and inaccurate response evaluations, the IWG proposed maintaining comparable pre- and on-study transfusion policies, with a maximum change in transfusion threshold of 1 g/dL before and during treatment. In addition, the IWG suggested that drug dosage should only be reduced if patients give 2 measurements of Hb level that exceed a predefined threshold; drug dosage should never be discontinued entirely.
Finally, the IWG amended the definition of “loss of response” to mean that the patient no longer meets IWG criteria and did not experience dose interruptions or concomitant infections, hemorrhagic events, and medications.
1. Platzbecker P, Fenaux L, Ades L, et al. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials [published online November 7, 2018]. Blood. doi: 10.1182/blood-2018-06-857102