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Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies

Despite remarkable advances in the treatment of multiple myeloma (MM) in the last decades, the prognosis of patients harboring highrisk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors have been demonstrated to partially ameliorate the pro...

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Autores principales: Mina, Roberto, Bonello, Francesca, Petrucci, Maria Teresa, Liberati, Anna Marina, Conticello, Concetta, Ballanti, Stelvio, Musto, Pellegrino, Olivieri, Attilio, Benevolo, Giulia, Capra, Andrea, Gilestro, Milena, Galieni, Piero, Cavo, Michele, Siniscalchi, Agostina, Palumbo, Antonio, Montefusco, Vittorio, Gaidano, Gianluca, Omedé, Paola, Boccadoro, Mario, Bringhen, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018137/
https://www.ncbi.nlm.nih.gov/pubmed/32107329
http://dx.doi.org/10.3324/haematol.2019.243428
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author Mina, Roberto
Bonello, Francesca
Petrucci, Maria Teresa
Liberati, Anna Marina
Conticello, Concetta
Ballanti, Stelvio
Musto, Pellegrino
Olivieri, Attilio
Benevolo, Giulia
Capra, Andrea
Gilestro, Milena
Galieni, Piero
Cavo, Michele
Siniscalchi, Agostina
Palumbo, Antonio
Montefusco, Vittorio
Gaidano, Gianluca
Omedé, Paola
Boccadoro, Mario
Bringhen, Sara
author_facet Mina, Roberto
Bonello, Francesca
Petrucci, Maria Teresa
Liberati, Anna Marina
Conticello, Concetta
Ballanti, Stelvio
Musto, Pellegrino
Olivieri, Attilio
Benevolo, Giulia
Capra, Andrea
Gilestro, Milena
Galieni, Piero
Cavo, Michele
Siniscalchi, Agostina
Palumbo, Antonio
Montefusco, Vittorio
Gaidano, Gianluca
Omedé, Paola
Boccadoro, Mario
Bringhen, Sara
author_sort Mina, Roberto
collection PubMed
description Despite remarkable advances in the treatment of multiple myeloma (MM) in the last decades, the prognosis of patients harboring highrisk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors have been demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with MM receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard-risk versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- risk versus high-risk patients, we observed similar progression-free survival (PFS) (3-year PFS: 52% vs. 43%, respectively; P=0.50), overall survival (OS) (3-year OS: 78% vs. 73%; P=0.38), and overall response rate (88% vs. 95%; P=0.47), with no statistical differences between the two groups. No difference in terms of PFS was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed MM patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted in similar PFS and OS as in standard-risk patients. (Registered at clinicaltrials.gov identifiers: NCT01857115 [IST-CAR-561] and NCT01346787 [IST-CAR-506].)
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spelling pubmed-80181372021-04-05 Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies Mina, Roberto Bonello, Francesca Petrucci, Maria Teresa Liberati, Anna Marina Conticello, Concetta Ballanti, Stelvio Musto, Pellegrino Olivieri, Attilio Benevolo, Giulia Capra, Andrea Gilestro, Milena Galieni, Piero Cavo, Michele Siniscalchi, Agostina Palumbo, Antonio Montefusco, Vittorio Gaidano, Gianluca Omedé, Paola Boccadoro, Mario Bringhen, Sara Haematologica Article Despite remarkable advances in the treatment of multiple myeloma (MM) in the last decades, the prognosis of patients harboring highrisk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors have been demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with MM receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard-risk versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- risk versus high-risk patients, we observed similar progression-free survival (PFS) (3-year PFS: 52% vs. 43%, respectively; P=0.50), overall survival (OS) (3-year OS: 78% vs. 73%; P=0.38), and overall response rate (88% vs. 95%; P=0.47), with no statistical differences between the two groups. No difference in terms of PFS was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed MM patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted in similar PFS and OS as in standard-risk patients. (Registered at clinicaltrials.gov identifiers: NCT01857115 [IST-CAR-561] and NCT01346787 [IST-CAR-506].) Fondazione Ferrata Storti 2020-02-27 /pmc/articles/PMC8018137/ /pubmed/32107329 http://dx.doi.org/10.3324/haematol.2019.243428 Text en Copyright© 2021 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Mina, Roberto
Bonello, Francesca
Petrucci, Maria Teresa
Liberati, Anna Marina
Conticello, Concetta
Ballanti, Stelvio
Musto, Pellegrino
Olivieri, Attilio
Benevolo, Giulia
Capra, Andrea
Gilestro, Milena
Galieni, Piero
Cavo, Michele
Siniscalchi, Agostina
Palumbo, Antonio
Montefusco, Vittorio
Gaidano, Gianluca
Omedé, Paola
Boccadoro, Mario
Bringhen, Sara
Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
title Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
title_full Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
title_fullStr Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
title_full_unstemmed Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
title_short Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
title_sort carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018137/
https://www.ncbi.nlm.nih.gov/pubmed/32107329
http://dx.doi.org/10.3324/haematol.2019.243428
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