Chromosome 1 abnormalities in elderly patients with newly diagnosed multiple myeloma treated with novel therapies

Abstract

Multiple myeloma is a plasma cell disorder characterized by malignant plasma cell infiltration in the bone marrow, serum and/or urine monoclonal protein and organ damage. The aim of this study was to investigate the impact of chromosome 1 abnormalities in a group of elderly patients (>65 years) with newly diagnosed multiple myeloma enrolled in the GIMEMA-MM-03-05 trial and treated with bortezomib, melphalan and prednisone or bortezomib, melphalan, prednisone and thalidomide followed by bortezomib and thalidomide maintenance. We also evaluated the link between chromosome 1 abnormalities and other clinical, genetic and immunophenotypic features by a multivariate logistic regression model. Interphase fluorescence in situ hybridization on immunomagnetically purified plasma cells and bone marrow multiparameter flow cytometry were employed. A multivariate Cox model showed that chromosome 1 abnormalities, age >75 years and a CD19(+)/CD117(-) immunophenotype of bone marrow plasma cells were independent risk factors for overall survival in elderly patients with newly diagnosed multiple myeloma. Moreover, a detrimental effect of thalidomide, even when administered in association with bortezomib, was observed in patients with abnormal chromosome 1 as well as in those with 17p deletion, while the benefit of adding thalidomide to the bortezomib-melphalan-prednisone regimen was noted in patients carrying an aggressive CD19(+)/CD117(-) bone marrow plasma cell immunophenotype. This trial was registered at www.clinicaltri-als.gov as #NCT01063179.

Copyright© Ferrata Storti Foundation.

Figures

Figure 1.

Abnormal chr1: Kaplan Meier curves and iFISH patterns. Clinical outcome of patients carrying abnormal chr1 [del(1p) and/or gain(1q)]: (A) Kaplan-Meier curve for PFS; (B) Kaplan-Meier curve for overall survival; (C) iFISH patterns for del(1p): two green signals in plasma cells with normal 1p and one green signal in plasma cells carrying 1p deletion; (D) iFISH patterns for gain(1q): two red signals in plasma cells with normal 1q and three or more signals in plasma cells carrying 1q gain. (Images captured with a Duet System, BioView Ltd, Israel).