t(11;14) status is stable between diagnosis and relapse and concordant between detection methodologies based on fluorescence <i>in situ</i> hybridization and next-generation sequencing in patients with multiple myeloma

Abstract

Multiple myeloma (MM) is associated with a wide variety of recurrent genomic alterations. The most common translocation in MM is t(11;14). In this retrospective, single-center, non-interventional study, patients’ bone marrow samples were examined at diagnosis and at relapse(s) following treatment with anti-myeloma regimens to determine whether t(11;14) status was stable over time. This stability cohort consisted of 272 patients, of whom 118 were t(11;14)-positive at diagnosis and 154 were negative. All patients in the stability cohort retained the same t(11;14) status at relapse that they had at diagnosis of MM. Sixteen patients who had t(11;14)-positive MM at diagnosis had multiple longitudinal assessments by fluorescence in situ hybridization (FISH) at relapse events and remained t(11;14)-positive across all timepoints. Patients who had t(11;14)-positive disease at diagnosis of monoclonal gammopathy of unknown significance or smoldering MM also retained t(11;14) positivity through MM diagnosis and relapse. The t(11;14) fusion patterns also remained constant for 90% of patients. For detection of t(11;14), results from FISH and next-generation sequencing (NGS) were compared to determine the rate of concordance between these two methods. This concordance cohort contained 130 patients, of whom 66 had t(11;14)-positive disease and 64 were t(11;14)-negative. In this sample set, the concordance between FISH- and NGS-based detection of t(11;14) was 100%. These results strongly suggest that the t(11;14) rearrangement remains stable during the full disease course in patients with MM and can be detected by FISH- and NGS-based methodologies.