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Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study

SIMPLE SUMMARY: Carfilzomib with dexamethasone is an important therapeutic option for patients with relapsed/refractory multiple myeloma. We sought to evaluate the effect of this regimen on the bone-related outcomes, which are associated with both quality of life and survival. Among 25 patients, les...

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Autores principales: Terpos, Evangelos, Ntanasis-Stathopoulos, Ioannis, Katodritou, Eirini, Kyrtsonis, Marie-Christine, Douka, Vassiliki, Spanoudakis, Emmanouil, Papatheodorou, Athanasios, Eleutherakis-Papaiakovou, Evangelos, Kanellias, Nikolaos, Gavriatopoulou, Maria, Makras, Polyzois, Kastritis, Efstathios, Dimopoulos, Meletios A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998249/
https://www.ncbi.nlm.nih.gov/pubmed/33809268
http://dx.doi.org/10.3390/cancers13061257
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author Terpos, Evangelos
Ntanasis-Stathopoulos, Ioannis
Katodritou, Eirini
Kyrtsonis, Marie-Christine
Douka, Vassiliki
Spanoudakis, Emmanouil
Papatheodorou, Athanasios
Eleutherakis-Papaiakovou, Evangelos
Kanellias, Nikolaos
Gavriatopoulou, Maria
Makras, Polyzois
Kastritis, Efstathios
Dimopoulos, Meletios A
author_facet Terpos, Evangelos
Ntanasis-Stathopoulos, Ioannis
Katodritou, Eirini
Kyrtsonis, Marie-Christine
Douka, Vassiliki
Spanoudakis, Emmanouil
Papatheodorou, Athanasios
Eleutherakis-Papaiakovou, Evangelos
Kanellias, Nikolaos
Gavriatopoulou, Maria
Makras, Polyzois
Kastritis, Efstathios
Dimopoulos, Meletios A
author_sort Terpos, Evangelos
collection PubMed
description SIMPLE SUMMARY: Carfilzomib with dexamethasone is an important therapeutic option for patients with relapsed/refractory multiple myeloma. We sought to evaluate the effect of this regimen on the bone-related outcomes, which are associated with both quality of life and survival. Among 25 patients, less than one third experienced a new skeletal-related event during treatment, even in the absence of any bone-targeted agent. Interestingly, there was a significant decrease in serum biomarkers of bone resorption, which was at least partially due to the sRANKL/OPG ratio reduction. Furthermore, Kd produced an increase in markers of bone formation. Importantly, these changes were independent of myeloma response to treatment. Therefore, the combination of carfilzomib and dexamethasone improves bone metabolism and bone health in patients with advanced multiple myeloma. ABSTRACT: Carfilzomib with dexamethasone (Kd) is a well-established regimen for the treatment of relapsed/refractory multiple myeloma (RRMM). There is limited information for the effects of Kd on myeloma-related bone disease. This non-interventional study aimed to assess skeletal-related events (SREs) and bone metabolism in patients with RRMM receiving Kd, in the absence of any bone-targeted agent. Twenty-five patients were enrolled with a median of three prior lines of therapy; 72% of them had evidence of osteolytic bone disease at study entry. During Kd treatment, the rate of new SREs was 28%. Kd produced a clinically relevant (≥30%) decrease in C-telopeptide of collagen type-1 (p = 0.048) and of tartrate-resistant acid phosphatase-5b (p = 0.002) at 2 months. This reduction was at least partially due to the reduction in the osteoclast regulator RANKL/osteoprotegerin ratio, at 2 months (p = 0.026). Regarding bone formation, there was a clinically relevant increase in osteocalcin at 6 months (p = 0.03) and in procollagen type I N-propeptide at 8 months post-Kd initiation. Importantly, these bone metabolism changes were independent of myeloma response to treatment. In conclusion, Kd resulted in a low rate of SREs among RRMM patients, along with an early, sustained and clinically relevant decrease in bone resorption, which was accompanied by an increase in bone formation, independently of myeloma response and in the absence of any bone-targeted agent use.
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spelling pubmed-79982492021-03-28 Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study Terpos, Evangelos Ntanasis-Stathopoulos, Ioannis Katodritou, Eirini Kyrtsonis, Marie-Christine Douka, Vassiliki Spanoudakis, Emmanouil Papatheodorou, Athanasios Eleutherakis-Papaiakovou, Evangelos Kanellias, Nikolaos Gavriatopoulou, Maria Makras, Polyzois Kastritis, Efstathios Dimopoulos, Meletios A Cancers (Basel) Article SIMPLE SUMMARY: Carfilzomib with dexamethasone is an important therapeutic option for patients with relapsed/refractory multiple myeloma. We sought to evaluate the effect of this regimen on the bone-related outcomes, which are associated with both quality of life and survival. Among 25 patients, less than one third experienced a new skeletal-related event during treatment, even in the absence of any bone-targeted agent. Interestingly, there was a significant decrease in serum biomarkers of bone resorption, which was at least partially due to the sRANKL/OPG ratio reduction. Furthermore, Kd produced an increase in markers of bone formation. Importantly, these changes were independent of myeloma response to treatment. Therefore, the combination of carfilzomib and dexamethasone improves bone metabolism and bone health in patients with advanced multiple myeloma. ABSTRACT: Carfilzomib with dexamethasone (Kd) is a well-established regimen for the treatment of relapsed/refractory multiple myeloma (RRMM). There is limited information for the effects of Kd on myeloma-related bone disease. This non-interventional study aimed to assess skeletal-related events (SREs) and bone metabolism in patients with RRMM receiving Kd, in the absence of any bone-targeted agent. Twenty-five patients were enrolled with a median of three prior lines of therapy; 72% of them had evidence of osteolytic bone disease at study entry. During Kd treatment, the rate of new SREs was 28%. Kd produced a clinically relevant (≥30%) decrease in C-telopeptide of collagen type-1 (p = 0.048) and of tartrate-resistant acid phosphatase-5b (p = 0.002) at 2 months. This reduction was at least partially due to the reduction in the osteoclast regulator RANKL/osteoprotegerin ratio, at 2 months (p = 0.026). Regarding bone formation, there was a clinically relevant increase in osteocalcin at 6 months (p = 0.03) and in procollagen type I N-propeptide at 8 months post-Kd initiation. Importantly, these bone metabolism changes were independent of myeloma response to treatment. In conclusion, Kd resulted in a low rate of SREs among RRMM patients, along with an early, sustained and clinically relevant decrease in bone resorption, which was accompanied by an increase in bone formation, independently of myeloma response and in the absence of any bone-targeted agent use. MDPI 2021-03-12 /pmc/articles/PMC7998249/ /pubmed/33809268 http://dx.doi.org/10.3390/cancers13061257 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Terpos, Evangelos
Ntanasis-Stathopoulos, Ioannis
Katodritou, Eirini
Kyrtsonis, Marie-Christine
Douka, Vassiliki
Spanoudakis, Emmanouil
Papatheodorou, Athanasios
Eleutherakis-Papaiakovou, Evangelos
Kanellias, Nikolaos
Gavriatopoulou, Maria
Makras, Polyzois
Kastritis, Efstathios
Dimopoulos, Meletios A
Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study
title Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study
title_full Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study
title_fullStr Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study
title_full_unstemmed Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study
title_short Carfilzomib Improves Bone Metabolism in Patients with Advanced Relapsed/Refractory Multiple Myeloma: Results of the CarMMa Study
title_sort carfilzomib improves bone metabolism in patients with advanced relapsed/refractory multiple myeloma: results of the carmma study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998249/
https://www.ncbi.nlm.nih.gov/pubmed/33809268
http://dx.doi.org/10.3390/cancers13061257
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