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 Zambello; Lorenzo De Paoli; Alessandra Romano; Antonio Palumbo; Vittorio Montefusco; Roman Hajek; Mario Boccadoro; Sara Bringhen

doi:10.3324/haematol.2019.220657

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 journal › Article › peer-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 language	English
Journal	Haematologica
DOIs	https://doi.org/10.3324/haematol.2019.220657
Publication status	E-pub ahead of print - Jun 27 2019

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Larocca, A., Mina, R., Offidani, M., Liberati, A. M., Ledda, A., Patriarca, F., Evangelista, A., Spada, S., Benevolo, G., Oddolo, D., Innao, V., Cangialosi, C., Bernardini, A., Musto, P., Amico, V., Fraticelli, V., Paris, L., Giuliani, N., Falcone, A. P., ... Bringhen, S. (2019). 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. Haematologica. https://doi.org/10.3324/haematol.2019.220657

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

In: Haematologica, 27.06.2019.

Research output: Contribution to journal › Article › peer-review

Larocca, A, Mina, R, Offidani, M, Liberati, AM, Ledda, A, Patriarca, F, Evangelista, A, Spada, S, Benevolo, G, Oddolo, D, Innao, V, Cangialosi, C, Bernardini, A, Musto, P, Amico, V, Fraticelli, V, Paris, L, Giuliani, N, Falcone, AP, Zambello, R, De Paoli, L, Romano, A, Palumbo, A, Montefusco, V, Hajek, R, Boccadoro, M & Bringhen, S 2019, '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', Haematologica. https://doi.org/10.3324/haematol.2019.220657

Larocca, Alessandra ; Mina, Roberto ; Offidani, Massimo ; Liberati, Anna Marina ; Ledda, Antonio ; Patriarca, Francesca ; Evangelista, Andrea ; Spada, Stefano ; Benevolo, Giulia ; Oddolo, Daniela ; Innao, Vanessa ; Cangialosi, Clotilde ; Bernardini, Annalisa ; Musto, Pellegrino ; Amico, Valeria ; Fraticelli, Vincenzo ; Paris, Laura ; Giuliani, Nicola ; Falcone, Antonietta Pia ; Zambello, Renato ; De Paoli, Lorenzo ; Romano, Alessandra ; Palumbo, Antonio ; Montefusco, Vittorio ; Hajek, Roman ; Boccadoro, Mario ; Bringhen, Sara. / 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. In: Haematologica. 2019.

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title = "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",

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).",

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

note = "Copyright {\textcopyright} 2019, Ferrata Storti Foundation.",

year = "2019",

month = jun,

day = "27",

doi = "10.3324/haematol.2019.220657",

language = "English",

journal = "Haematologica",

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TY - JOUR

T1 - First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients

T2 - a pooled analysis of two randomized trials

AU - Larocca, Alessandra

AU - Mina, Roberto

AU - Offidani, Massimo

AU - Liberati, Anna Marina

AU - Ledda, Antonio

AU - Patriarca, Francesca

AU - Evangelista, Andrea

AU - Spada, Stefano

AU - Benevolo, Giulia

AU - Oddolo, Daniela

AU - Innao, Vanessa

AU - Cangialosi, Clotilde

AU - Bernardini, Annalisa

AU - Musto, Pellegrino

AU - Amico, Valeria

AU - Fraticelli, Vincenzo

AU - Paris, Laura

AU - Giuliani, Nicola

AU - Falcone, Antonietta Pia

AU - Zambello, Renato

AU - De Paoli, Lorenzo

AU - Romano, Alessandra

AU - Palumbo, Antonio

AU - Montefusco, Vittorio

AU - Hajek, Roman

AU - Boccadoro, Mario

AU - Bringhen, Sara

PY - 2019/6/27

Y1 - 2019/6/27

N2 - 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).

AB - 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).

U2 - 10.3324/haematol.2019.220657

DO - 10.3324/haematol.2019.220657

M3 - Article

C2 - 31248973

JO - Haematologica

JF - Haematologica

SN - 0390-6078

ER -