Abstract 2714: Development of a novel Ikaros/Aiolos transcriptional signature and correlation with patient response in multiple myeloma patients treated with CELMoDs.

Key Points

• The study aims to create a quantitative Ikaros/Aiolos activity score to evaluate its correlation with patient responses to CELMoDs in multiple myeloma.
• Identified Ikaros binding targets using CUT&RUN and ChIP-seq.
• Analyzed transcriptional changes when exposed to immunomodulatory drugs.
• Performed differential expression analysis using DESeq2.
• Developed an Ik activity score based on RNA-seq paired samples from patients.
• Validated associations of the Ik activity score with progression-free survival.
• Significantly lower Ik activity scores were observed in on-treatment samples compared to screening.
• A trend of greater change in activity score was noted among responders to IBER and MEZI.
• Higher changes in activity scores were significantly associated with longer progression-free survival.
• Similar associations with higher Ik degradation percentage favoring longer progression-free survival were seen in IHC data.