EZH2 targeting induces CD38 upregulation and response to anti-CD38 immunotherapies in multiple myeloma
Djamila Chemlal, Emmanuel Varlet, Amélie Machura, Sara Ovejero, Guilhem Requirand, Nicolas Robert, Guillaume Cartron, Elina Alaterre, Caroline Bret, Laure Vincent, Charles Herbaux, Giacomo Cavalli, Angélique Bruyer, Hugues de Boussac, Jérôme Moreaux
Abstract
Multiple myeloma (MM) is a frequent hematological malignancy characterized by the accumulation of tumor plasma cells within the bone marrow, and major biological and clinical heterogeneity. Genome sequencing studies have revealed considerable heterogeneity and genomic instability, a complex mutational landscape and a branching pattern of clonal evolution [ 1 ]. Despite important improvement in patients outcome in the last decade with the use of next generation IMiDs (immunomodulatory drugs), proteasome inhibitors, and the introduction of CD38-targeting immunotherapies patients eventually relapse [ 1 ].