Prognostic impact of translocation t(14;16) in multiple myeloma according to the presence of additional genetic lesions
Anaïs Schavgoulidze, Aurore Perrot, Titouan Cazaubiel, Xavier Leleu, Lydia Montes, Caroline Jacquet, Karim Belhadj, Sabine Bréchignac, Laurent Frenzel, Thomas Chalopin, Philippe Rey, Jean-Marc Schiano de Collela, Mamoun Dib, Denis Caillot, Margaret Macro, Jean Fontan, Laure Buisson, Luka Pavageau, Murielle Roussel, Salomon Manier, Mohamad Mohty, Ludovic Martinet, Hervé Avet‐Loiseau, Jill Corre
Abstract
Patients with multiple myeloma (MM) have experienced a markedly improved survival over the past 25 years, thanks in part to the availability of new drugs [ 1 ]. However, a subgroup of patients known as high-risk patients continues to represent an unmet medical need, with an overall survival of less than three years [ 2 ]. In the context where we aim to design clinical trials dedicated to high-risk myeloma patients, these patients must be accurately identified from diagnosis. Given the major prognostic role of cytogenetics in myeloma, the Revised International Staging System has included three cytogenetic abnormalities (CA) in 2015: the deletion 17p and the translocations t(4;14) and t(14;16), along with LDH level [ 3 ]. The t(14;16) is also considered as a high-risk factor in the m-SMART risk stratification [ 4 ]. Whereas le prognostic role of t(4;14) and deletion 17p is widely accepted, the independent prognostic impact of t(14;16) has been a matter of debate [ 5 , 6 , 7 , 8 ]. This rare translocation (around 3.5% of MM patients) involves the IGH locus and the oncogene c-MAF, whose overexpression has been shown to mediate innate resistance to proteasome inhibitors [ 9 ]. In addition, t(14;16) MM cells clearly display a much higher mutations number and a higher APOBEC-related mutational process than non-t(14;16) MM cells [ 10 , 11 ].