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

Abstract

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

Copyright© 2020 Ferrata Storti Foundation.

Figures

Figure 1.
Figure 1.
Subgroup analysis of progression-free survival in the intention-to-treat population for patients treated with VMP or Rd-R. VMP: bortezomib-melphalan-prednisone; Rd-R: lenalidomide-dexamethasone followed by lenalidomide maintenance; HR: hazard ratio; 95% CI: 95% confidence interval; ISS: International Staging System.
Figure 2.
Figure 2.
Subgroup analysis of overall survival in the intention-to-treat population for patients treated with VMP or Rd-R. VMP: bortezomib-melphalan-prednisone; Rd-R: lenalidomide-dexamethasone followed by lenalidomide maintenance; HR: hazard ratio; 95% CI: 95% confidence interval; ISS: International Staging System.

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