Immune Modulation in MDS: Our Core Strategies Need to Change

Myelodysplastic Syndrome News

Immune Modulation in MDS: Our Core Strategies Need to Change
MyelodysplasiaMyelodysplastic Syndrome (MDS)Biologic Therapy
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Experts reassess endpoints, patient selection, targets, and timing for the development of successful immune-based treatments for myelodysplastic syndromes.

MILAN — Immune-based treatments continue to fall short in myelodysplastic syndrome s . Now, experts from the European Hematology Association’s Specialized Working Group on MDS here at the EHA 2025 Congress are reevaluating their core strategies, from clinical trial endpoints to patient selection and timing.

The CANFIRE trial enrolled 11 patients treated for 6 months, while LUCAS included 36 patients treated for 4 months. Both studies failed to meet their primary endpoint, hematologic improvement in erythroid cells per International Working Group 2018 criteria, by the end of the treatment period. Kubasch suggested that future trials should incorporate patient-reported outcomes and quality-of-life metrics as co-primary endpoints. “We may focus on composite endpoints combining various parameters, such as hematologic trends, biomarker shifts, molecular remission or stability, and, of course, patient-reported benefits.”of bone marrow CD34+ cells from 183 MDS patients that identified two immune subtypes based on the expression of six genes — including, the target of emavusertib.

Importantly, she emphasized that immune dysfunction in MDS is dynamic. “It changes during the course of the disease,” she said. Therefore, precise immune profiling at both the subtype and patient level is needed. Optimization of immunosuppressive therapy is hampered by the lack of prospective randomized trials, heterogeneity in study populations, poor characterization of immune abnormalities, and the need for integration with novel agents. “It is not one cure for all,” she said.

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Myelodysplasia Myelodysplastic Syndrome (MDS) Biologic Therapy Biologics Hematology Haematology Transplant Evaluation Patient Selection Bone Marrow Medulla Ossea Biomarker Biological Marker Multi-Biomarker Disease Activity MBDA Multibiomarker Disease Activity Bones Hospitals Immunomodulator Lenalidomide Immunosuppressive Therapy Immunosuppressive Agents

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