Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (Δ13) in multiple myeloma: An Eastern Cooperative Oncology Group study

Chromosome 13 abnormalities (Δ13) have been associated with an unfavorable prognosis in patients with multiple myeloma (MM). The significance of this has been unresolved because of diverse methods of detection and heterogeneous groups of patients. We conducted a study of Δ13 in patients entered into the Eastern Cooperative Oncology Group trial E9486/E9487. Patients with newly diagnosed MM (median follow-up of survivors > 100 months) were studied for Δ13, using bone marrow samples obtained at study enrollment. We used interphase fluorescence in situ hybridization with the probes LSII3 (Rb)/D13S319 with simultaneous immunofluorescence detection of bone marrow plasma cells (PCs). We detected Δ13 in 176 of 325 (54%) evaluable patients. Patients with Δ13 were more likely to have a serum monoclonal protein at a concentration ≤ 1 g/dl (22 versus 13%; P = 0.04), light-chain-only MM (19.3 versus 10.8%; P = 0.04), κ light chain (42 versus 28%; P = 0.027), stage III (56 versus 42%; P = 0.014), and be female (60 versus 50%; P = 0.087). The PC labeling index and Δ13 correlated (P = 0.03). Patients with Δ13 were less likely to respond to treatment (74 versus 63%; P = 0.041) and had a significantly shorter median overall survival (34.9 versus 51 months; P = 0.021). The association of Δ13 and survival remained an independent prognostic variable in a regression model. Among patients with Δ13, those receiving IFN had a worse overall survival that those not receiving the medication (P = 0.03). The presence of Δ13 is an important and independent adverse prognostic factor in newly diagnosed MM and is associated with specific biological features.