Chromosome 1 abnormalities and clinical outcomes in multiple myeloma in the era of novel agents.

Abstract

8044 Background: Abnormalities of chromosome 1 (C1A) are common genetic mutations in patients (pts) with Multiple Myeloma (MM). While several small studies have reported worse outcomes for C1A, the prevalence, real-world treatment and outcomes for pts with C1A are unknown. Methods: We used the Flatiron Health Electronic Health Record (EHR)-derived database to identify pts with newly diagnosed MM from 01/2011 to 03/2018 with Fluorescence In situ Hybridization (FISH) testing within 90 days of diagnosis and defined lines of therapy. We identified pts with C1A and other high-risk mutations (HRM; 17p deletion, t14;16 and t4;14). Pts were followed until 3/31/2018 or death. The primary outcome was overall survival (OS). We used Kaplan Meier methods and compared OS for pts with/without C1A using log-rank tests stratified for HRM. We used Cox regression analysis to compare OS across groups, adjusting for age, gender, performance status, stage, HRM and treatment (triple regimen vs other). Results: The total sample included 3,578 pts: median age at diagnosis was 69 yrs (IQR 31-85), with 54% males and 60% whites. IgG(57%) and IgA(22%) were the most common M-protein subtypes. At baseline, 844 (24%) had C1A. Pts with C1A had higher stage (ISS III 35% vs 26%; p < 0.01) and other HRM (27% vs 14%, p < 0.01). Common first line-therapies included bortezomib(V), lenalidomide(R) and dexamethasone (D) (35%), RD (20%) followed by VD(15%). Use of VRD was higher with C1A vs without (40% vs 33% respectively, p < 0.01). Median OS was 66.9 months for the entire cohort and was lower for pts with C1A vs without (median OS 46.6 vs 70.1 months; log rank p < 0.01). Multivariable Cox survival analysis showed that C1A was independently associated with worse OS (adjusted HR 1.64; 95% CI 1.23-2.19); p < 0.01). Other predictors of worse survival included older age, black ethnicity, higher ISS stage, poor performance status and HRM. Conclusions: In this large study of real-world practice, C1A was associated with inferior OS independent of other HRM, despite higher use of VRD. Future studies are needed to assess whether specific regimens improve outcomes for C1A compared to patients without HRM.