Incidence and Prognostic Value of Chromosomal Abnormalities in Elderly Patients with myeloma: The IFM Experience on 1095 Patients
Authors: Avet-Loiseau Hervé , Hulin Cyrille , Campion Loic , Roussel Murielle , Marit Gerald , Caillot Denis , Stoppa Anne-Marie , Pegourie Brigitte , Fuzibet Jean-Gabriel , Chateleix Carine , Royer Bruno , Traulle Catherine , Decaux Olivier , Benboubker Lotfi , Casassus Philippe , Macro Margaret , Mathiot Claire , Kolb Brigitte , Fermand Jean-Paul , Facon Thierry 
Published: October 2019

Abstract
Abstract 994
The outcome of patients with multiple myeloma (MM) is highly influenced by chromosomal abnormalities, and especially translocation t(4;14) and del(17p). However, these data have been mostly demonstrated in young patients, less than 65 years of age, treated with high-dose chemotherapy. Almost no data is available in elderly patients. In order to address this issue, we retrospectively analyzed patients over 66 years old, treated with various regimens in the Intergroupe Francophone du Myélome (IFM). Since chromosomal abnormalities are centrally analyzed in the IFM, we focused our analyses on 1890 patients (age=65–94, median=71 y). The patients were divided in two groups: 66–74 y (1239 patients) and over 75 y (651 patients). We first analyzed the incidence of the following abnormalities: del(13), del(17p) (defined by a deletion present in at least 60% of the plasma cells), and t(4;14). The incidence of del(13) was 43.6% in the first group, and 37% in the second one (p=.007). For del(17p), the incidences were 5.9% and 6.1%, respectively (p=NS). Finally, for t(4;14), the incidences were 10.9% and 8.3%, respectively (p=.09). When compared to patients < 65 y, we observed a highly significant lower incidence of t(4;14) in elderly patients (14% vs 10.9% vs 8.3%, p<.0001), vs no significant difference for del(13) and del(17p). Treatment and follow-up data were available for 1095 of these patients. Fifteen % of the patients were treated with high-dose chemotherapy (median age=66 y), 246 received melphalan-prednisone (MP), 434 receined MP-thalidomide (MPT), the others receiving various schemas, including MP-bortezomib (84 patients), lenalidomide-dexamethasone (118 patients), or intermediate-dose melphalan (45 patients). Global prognostic analyses showed that both t(4;14) and del(17p) influenced both the progression-free survival (PFS) and overall survival (OS). Even after stratification on treatment schema, both chromosomal abnormalities retained prognostic value: <10−6 for both t(4;14) and del(17p) for PFS, and <10−4 and <10−6 for OS, respectively. When restricted to the largest treatment group, i.e., patients treated with MPT, the respective p values were <10−4 and <0.002 for PFS, and <0.006 and <10−3 for OS. To conclude, this is by far the largest series analyzing the prognostic impact of chromosomal abnormalities in elderly patients. As demonstrated in younger patients, both t(4;14) and del(17p) negatively impact the PFS and OS survival of these elderly patients.

Disclosures:
Hulin: Janssen-Cilag: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Facon:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria.