In myelodysplastic syndromes (MDS), chronic inflammation driven by the innate immune system plays a key role in disease progression. Signal Transducer and Activator of Transcription (STAT) and Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) are critical mediators in this process, where dysregulated signaling leads to aberrant hematopoiesis and the promotion of a pro-inflammatory environment that supports the clonal expansion of malignant cells.

This podcast episode features experts Andrew Wei, MBBS, PhD, Alfred Hospital and Monash University, Melbourne, Australia, Aditi Shastri, MD, Montefiore Medical Center, Bronx, NY, Uwe Platzbecker, MD, University of Leipzig, Leipzig, Germany, and Amer Zeidan, MBBS, Yale University and Yale Cancer Center, New Haven, CT. They discuss the role of inflammation and immune interventions from the 2nd International Workshop on Myelodysplastic Syndromes and Myeloproliferative Neoplasms (iwMDS) 2024, held in Boston, MA. They focus on the targeting of STAT and IRAK4, the pivotal Phase III STIMULUS-MDS2 trial (NCT04266301) of sabatolimab, and lessons that can be learned from clinical trial failures.