Achieving Clinical Remission Improves Survival of Patients With MDS, But Timing of Transplant Remains Key

New data from the International Consortium for MDS (icMDS) Validate Database showed that achieving clinical remission with hypomethylating agents (HMAs) enhances survival for patients with high-risk myelodysplastic syndrome (MDS), particularly those not undergoing transplants.

High-risk MDS is associated with poor outcomes, making the assessment of treatment response critical. Benjamin Rolles, MD, Brigham and Women’s Hospital, Boston, Massachusetts, shared a new analysis from the icMDS Validate Database, shedding light on the survival implications of achieving composite complete response (CR) with HMA therapy.¹ This global database includes more than 4,000 cases of myeloid malignancies from 30 MDS centers worldwide.

The study analyzed 762 patients with high-risk MDS treated with HMA-based therapies. Patients were stratified by baseline molecular risk using the International Prognostic Scoring System-Molecular (IPSS-M), and treatment responses were classified according to the updated International Working Group 2023 criteria.^2,3

About 37% of the patients in the study achieved composite CR, encompassing various remission levels including complete response (CR) and CR with partial hematologic recovery. Across all groups of patients, both achieving composite CR and having an allogeneic stem cell transplant (allo-SCT) significantly improved overall survival (OS). Among patients who did not undergo transplants, achieving composite CR independently improved OS across all risk categories, with median survival extending by more than double in some groups. In patients who underwent allo-SCT, treatment response did not provide any additional survival benefit within any baseline molecular risk groups. However, baseline molecular risk, defined by IPSS-M, was a strong predictor of OS. Optimal timing of allo-SCT, defined by patient age and IPSS-M risk, emerged as a critical factor. Only 34% of patients who had a transplant underwent the procedure within the recommended timeframe, but those who did experienced significantly better survival outcomes. Among patients achieving composite CR before transplant, those who underwent a transplant in the optimal timeframe had an OS of 6.2 years versus 2.5 years for those who underwent a transplant outside the optimal timeframe.

These findings carry immediate implications for clinical practice and highlight the importance of adhering to optimal transplant timing. Dr. Rolles concluded: “The time to transplant remained a critical factor to improve survival, even in patients who responded to HMA therapy prior to transplantation.”

References

1. Rolles B, Bewersdorf JP, Kewan T, et al. Impact of response to hypomethylating agent-based therapy on survival outcomes in the context of baseline clinical-molecular risk and transplant status in patients with myelodysplastic syndromes/neoplasms (MDS): an analysis from the International Consortium for MDS (icMDS) Validate Database. Abstract #664. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.