First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: a pooled analysis of two randomized trials

Alessandra Larocca, Roberto Mina, Massimo Offidani, Anna Marina Liberati, Antonio Ledda, Francesca Patriarca, Andrea Evangelista, Stefano Spada, Giulia Benevolo, Daniela Oddolo, Vanessa Innao, Clotilde Cangialosi, Annalisa Bernardini, Pellegrino Musto, Valeria Amico, Vincenzo Fraticelli, Laura Paris, Nicola Giuliani, Antonietta Pia Falcone, Renato ZambelloLorenzo De Paoli, Alessandra Romano, Antonio Palumbo, Vittorio Montefusco, Roman Hajek, Mario Boccadoro, Sara Bringhen

Research output: Contribution to journalArticlepeer-review

Abstract

Bortezomib-melphalan-prednisone and continuous lenalidomide-dexamethasone represent the standard treatment of transplant-ineligible, newly diagnosed, multiple myeloma patients. To date, no randomized trial has compared bortezomib-melphalan-prednisone to lenalidomide-dexamethasone, and there is no evidence of the optimal treatment for newly diagnosed multiple myeloma, particularly in high-risk cytogenetic patients (del(17p), t(4;14) or t(14;16)). We pooled together data from newly diagnosed myeloma patients treated with bortezomib-melphalan-prednisone or lenalidomide-dexamethasone induction followed by lenalidomide maintenance 10 mg enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate their efficacy in different patient subgroups, focusing on standard and high-risk cytogenetics. Overall, 474 patients were analyzed (bortezomib-melphalan-prednisone: 257 patients; lenalidomide-dexamethasone followed by lenalidomide maintenance: 217 patients). No difference in progression-free survival (Hazard Ratio: 0.96) and overall survival (Hazard Ratio: 1.08) was observed between bortezomib-melphalan-prednisone and lenalidomide-dexamethasone followed by lenalidomide in standard-risk, while a reduction in the risk of progression (Hazard Ratio: 0.54) and death (Hazard Ratio: 0.73) was seen in high-risk patients treated with bortezomib-melphalan-prednisone vs. lenalidomide-dexamethasone followed by lenalidomide. In particular, standard risk patients >75years benefited less from bortezomib-melphalan-prednisone than lenalidomide-dexamethasone followed by lenalidomide (Hazard Ratio for progression-free survival: 0.96; Hazard Ratio for overall survival: 1.81). In this non-randomized analysis, bortezomib-melphalan-prednisone and lenalidomide-dexamethasone followed by lenalidomide were equally effective in younger (≤75years), standard-risk patients, while older ones (>75years) benefited more from lenalidomide-dexamethasone followed by lenalidomide. In high-risk patients, bortezomib-melphalan-prednisone improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196).

Original languageEnglish
JournalHaematologica
DOIs
Publication statusE-pub ahead of print - Jun 27 2019

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