Clinical Outcomes According to Genomic Abnormalities in 566 Newly Diagnosed Multiple Myeloma Patients Treated with Bortezomib-Based Regimens

• Published in: Blood 2009-11, Vol.114 (22), p.1868-1868
• Main Authors: Cavo, Michele, Bringhen, Sara, Testoni, Nicoletta, Omedè, Paola, Marzocchi, Giulia, Ruggeri, Marina, Durante, Sandra, Di Raimondo, Francesco, Rossi, Davide, Gorgone, Ausilia, Patriarca, Francesca, Petrucci, Maria Teresa, Buttignol, Silvia, Levi, Anna, Offidani, Massimo, Nozzoli, Chiara, Ria, Roberto, Olivero, Barbara, Galli, Monica, Montefusco, Vittorio, Callea, Vincenzo, Falcone, Antonietta, De Vivo, Antonio, Boccadoro, Mario, Terragna, Carolina, Palumbo, Antonio
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.1868.1868

Abstract 1868 Poster Board I-893 Bortezomib was initially reported to overcome the poor prognosis related to the presence of del(13q) in patients with advanced refractory/relapsed multiple myeloma (MM). However, more recent evaluations of genomic aberrations in MM provided demonstration that only t(4;14) and del(17p) retained prognostic value for both EFS and OS, thus identifying a subgroup of patients at high risk of progression or death. The combination of bortezomib with melphalan and prednisone, actually licensed as first-line therapy for MM patients who are not eligible for autologous stem-cell transplantation (ASCT), showed comparable activities in terms of time to progression and OS among patients with or without high-risk cytogenetic profiles. However, the number of high-risk patients analyzed was very limited, due to the low frequency of these genomic abnormalities. To more carefully assess the role of bortezomib in patients with high-risk cytogenetics [(e.g. carrying t(4;14) and/or del(17p)], we performed a post-hoc analysis of two phase 3 studies of first-line bortezomib-based regimens for the treatment of a large series of MM patients. Both studies are actually conducted by the Italian Myeloma Network GIMEMA. The activity of three different bortezomib-based regimens in terms of achievement of best high-quality response (immunofixation negative CR) and PFS was analyzed. Regimens evaluated were bortezomib-thalidomide-dexamethasone (VTD), bortezomib-melphalan-prednisone (VMP) and bortezomib-melphalan-prednisone-thalidomide (VMPT). VTD was followed by ASCT. Treatment details are as follows: VTD (Bortezomib, 1.3 mg/m2 twice-weekly, every 21/d cycle; Thalidomide, 200 mg/d; Dexamethasone, 320 mg/cycle); VMP (Bortezomib 1.3 mg/m2 on d 1, 8, 15 and 22, every 35/d cycle; Melphalan, 9 mg/m2 on d 1 through 4, every cycle; Prednisone, 60 mg/m2 on d 1–4 of each cycle); VMPT (VMP, as previously described; Thalidomide, 50 mg/d). A total of 566 patients for whom results of interphase FISH analysis at diagnosis were available for the presence or absence of del(13q) and/or t(4;14) and/or del(17p), were included in the present study. Three cytogenetic subgroups of patients were identified, including those without genomic abnormalities (group 1; n=257), those with del(13q) alone (group 2; n=162) and those who carried t(4;14) and/or del(17p) with or without del(13q) (group 3; n=147). For the purpose of the present analysis, clinical outcomes (e.g. CR rate and PFS) o