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ASH 2021 | 2q loss associated with lenalidomide and pomalidomide resistance in myeloma

Pharmacogenetic screening has identified several genes essential for immunomodulatory drug (IMiD) sensitivity in vitro. Sarah Gooding, MD PhD, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, discusses the findings of a study assessing the clinical relevance of copy loss of these genes. Candidate genes consistently identified as essential for lenalidomide or pomalidomide function in screens were shortlisted. Using whole genome sequencing (WGS) data from a large set of advanced and drug resistant multiple myelomas, the incidence of changes in these candidate genes was assessed. The 2q region was identified as a novel region of interest; proportion of loss of this region increased between newly diagnosed, lenalidomide-refractory, and lenalidomide-then-pomalidomide-refractory states. Additionally, in a cohort of patients with WGS data available before and after acquiring IMiD resistance, loss of the 2q region was acquired in 21%. Dr Gooding explains the relevance of the 2q region to IMiD function. These findings suggest 2q loss may drive a therapy-specific clonal advantage in myeloma. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.