MM-245 landscape of genomic aberrations in multiple myeloma

Abstract

Introduction Risk stratification of multiple myeloma (MM) is based on genetic abnormalities detected by fluorescence in situ hybridization (FISH). High-risk MM is defined as having at least one of the mutations related with poor prognosis: t(4::14), t(14::16), t(14::20), del 17p, p53 mutation, gain 1q, and del 1p. The presence of any 2 high-risk factors is considered double-hit myeloma (DHM); 3 or more high-risk factors is triple-hit myeloma (THM). Aim & Objective The aim of this study was to evaluate genomic aberrations in newly diagnosed multiple myeloma (NDMM) patients with respect to high-risk cytogenetic features including DHM and THM. Materials and Methods: The case records of NDMM patients were identified, and the information regarding baseline characteristics, cytogenetics, therapy, and outcomes was noted. Result The study analyzed 537 NDMM cases (343 male, 194 female, median age 58 years, range 23–87 years). IgG MM was found in 333 (62.0%) cases, IgA in 76 (14.2%), light chain MM in 111 (20.7%), IgM in 2 (0.4%), and IgD in one (0.2%). Revised-ISS 1 score was exhibited by 9.4%, R-ISS 2 in 61.6%, and R-ISS 3 in 29.0% cases. Status of t(4::14), t(14::16), t(14::20), del 17p, p53 mutation, gain 1q, and del 1p was available in 323 cases, out of which single high-risk genetic abnormality was observed in 93 (28.8%) cases. DHM and THM was identified in 46 (14.2%) patients: 35 with DHM and 11 with THM (32 male, 16 female, median age 56 years, range 33–72 years). In DHM, the most common cytogenetic combination was t(4::14) with gain of 1q (18 patients, 39.1%). In THM, the most common combination was t(4::14) with del 1p and gain 1q (6 patients, 54.6%). The treatment outcomes were inferior in patients with DHM and THM. The overall survival (OS) in THM (median OS: 7 months) was significantly lower as compared to DHM (median OS: 35 months, P=0.032) and single-hit MM (median OS: 41 months, P=0.038). Conclusions DHM and THM constitute 14.2% of NDMM cases, and their presence indicates a high-risk course of disease and shorter survival, consequently indicating necessity of intensive treatment/clinical trial options with new treatment modalities as early as possible.