Inobrodib Treatment Synergises with Imids to Epigenetically Downregulate IRF4 Expression in Drug-Resistant Myeloma (IMS 2026) - Sep 11, 2026 - Abstract #PA-259; Pres time: Sep 24, 2026; "Standard-of-care immunomodulatory drugs (IMiDs), e.g. pomalidomide (Pom), target the TFs IKZF1/3 to the E3 ubiquitin ligase CRBN for degradation, resulting in IRF4 downregulation...The P300/CBP inhibitor Inobrodib (Ino), in combination with Pom and dexamethasone, is currently showing promise in phase IIa clinical trials for RRMM...Ino-resistant cells displayed tolerance to both Pom and the CELMoD mezigdomide, and Pom-resistant cells were tolerant to Ino... Our findings implicate epigenetic rewiring of IRF4 expression as a common mechanism of resistance to Ino and IMiDs. However, combined treatment with Pom and Ino is able to downregulate IRF4 expression in resistant cells, depending on the presence of functional CRBN. Therapeutically, this indicates that addition of Ino to Pom treatment may help resensitise IMiD-resistant RRMM patients."
Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • ANXA5 • CRBN • IKZF1 • IRF4
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Jason Taslim1; Sophie S. Ball1; Katrina FordworHepburn1; Laurence Gesman1; Thomas Milne2; Aristeidis Chaidos1; Anastasios Karadimitris1; Nicholas T. Crump1
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