Higher-Risk MDS Trials Analysis: Complete Response is Most Relevant Outcome Measure

Researchers have performed statistical analysis of data from clinical trials in higher-risk myelodysplastic syndromes (MDS) to see if any relationships exist between outcome measures in this disease. They presented their findings at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

The investigative team from the US Food and Drug Administration (FDA) in Silver Spring, Maryland, concluded that “[complete response (CR)] remains the response endpoint associated with greatest long-term benefit and that [event-free survival (EFS)], as defined, is not an established surrogate for [overall survival (OS)], but is worthy of further study.”

The analysis included nine randomized, controlled, multicenter trials submitted to the FDA as part of New Drug Applications and Investigational New Drug Applications for MDS between 2000 and 2024. They had a combined patient population of 2,053 patients, which had a median age of 71 years, was 66% male, and 75% White. Two of the trials lacked active controls.

Of the seven studies with active controls, the investigators performed a trial-level meta-analysis of OS versus CR and OS versus CR plus partial response (PR). Weighted linear regression analysis found the association between OS and CR and between OS and CR plus PR to be weak, with coefficients of determination of 0.40 and 0.33, respectively.

Across all trials, the investigators calculated a moderate association between OS and EFS, with a coefficient of determination of 0.82. At the patient level, they also found that patients who achieved a response of CR had better OS compared with those who had a PR response, a hematologic improvement response, or no response, with hazard ratios of 0.70, 0.56, and 0.33, respectively.

The investigators noted that “[o]ur results are limited by the small number of trials, lack of an active comparator in two trials, and non-standardized response criteria across trials.”

Reference

Kim N, Wang X, Bulatao I, et al. Response rate, event-free survival (EFS), and overall survival in higher-risk myelodysplastic syndromes (MDS): U.S. Food and Drug Administration (FDA) trial-level and patient-level analyses. Abstract #1829. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.