Cereblon gene variants and clinical outcome in multiple myeloma patients treated with lenalidomide

Phoebe A Huang, Shaunna L Beedie, Cindy H Chau, David J Venzon, Sheryl Gere, Dickran Kazandjian, Neha Korde, Sham Mailankody, Ola Landgren, William D Figg, Phoebe A Huang, Shaunna L Beedie, Cindy H Chau, David J Venzon, Sheryl Gere, Dickran Kazandjian, Neha Korde, Sham Mailankody, Ola Landgren, William D Figg

Abstract

Carfilzomib-lenalidomide-dexamethasone (KRd) therapy has yielded promising results in patients with newly diagnosed multiple myeloma (NDMM). Cereblon (CRBN) is the direct molecular target of lenalidomide and genetic polymorphisms in CRBN have been associated with lenalidomide efficacy. In this study, we assessed the correlation of five single nucleotide variants (SNVs) in the CRBN gene with clinical response and outcomes in patients with NDMM administered KRd therapy with lenalidomide maintenance, achieving favorable trial endpoints in a prospective Phase II study (NCT01402284). Of the observed SNVs, no associations with KRd therapy response were found in this patient cohort, although strong trends in hypoalbuminemia grade and hyperbilirubinemia grade emerged across the CRBN rs1672753 genotype (P = 0.0008) and the rs1714327 genotype (P = 0.0010), respectively. Our results do not provide conclusive support for the predictive utility of CRBN gene polymorphisms as potential biomarkers of clinical response to lenalidomide-based therapy in our patient population. However, these findings remain to be validated in prospective studies using larger patient populations.

Conflict of interest statement

O.L. receives grant support from NIH, FDA, MMRF, IMF, LLS, Perelman Family Foundation, Rising Tides Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, and Karyopharm. He is a member of the following Honoraria/Advisory Boards: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, and Pfizer. He also serves as Chairman for “Medscape Myeloma” (2014-ongoing) and is a member of the Independent Data Monitoring Committee (IDMC) for Takeda, Merck, Janssen, and Theradex. All other authors declare no potential conflict of interest.

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Source: PubMed

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