Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma

Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). We developed a mathematical model to assess the prognostic value of serum MC...

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Autores: Tamariz-Amador, Luis-Esteban, Rodriguez-Otero, Paula, Jiménez-Ubieto, Ana, Rosiñol, Laura, Oriol, Albert, Rios, Rafael, Sureda, Anna, Blanchard, María-Jesús, Hernández, Miguel-Teodoro, Cabañas Perianes, Valentin, Jarque, Isidro, Bargay Lleonart, Joan, Gironella, Mercedes, de Arriba, Felipe, Palomera, Luis, Gonzalez-Montes, Yolanda, Martí, Josep M, Krsnik, Isabel, Arguiñano, José María, González, María Esther, Casado, Luis Felipe, González-Rodriguez, Ana Pilar, López-Anglada, Lucía, Puig, Noemi, Cedena, Maria Teresa, Paiva, Bruno, Mateos, Maria-Victoria, San Miguel, Jesus F., Lahuerta, Juan-José, Bladé, Joan, Trocóniz, Iñaki F
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/18621
Acesso em linha:https://hdl.handle.net/20.500.13003/18621
Access Level:acceso abierto
Palavra-chave:Prognosis
Multiple Myeloma
Neoplasm, Residual
Treatment Outcome
Humans
Antineoplastic Combined Chemotherapy Protocols
Paraproteins
Resultado del Tratamiento
Humanos
Protocolos de Quimioterapia Combinada Antineoplásica
Pronóstico
Mieloma Múltiple
Paraproteínas
Neoplasia Residual
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spelling Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple MyelomaTamariz-Amador, Luis-EstebanRodriguez-Otero, PaulaJiménez-Ubieto, AnaRosiñol, LauraOriol, AlbertRios, RafaelSureda, AnnaBlanchard, María-JesúsHernández, Miguel-TeodoroCabañas Perianes, ValentinJarque, IsidroBargay Lleonart, JoanGironella, Mercedesde Arriba, FelipePalomera, LuisGonzalez-Montes, YolandaMartí, Josep MKrsnik, IsabelArguiñano, José MaríaGonzález, María EstherCasado, Luis FelipeGonzález-Rodriguez, Ana PilarLópez-Anglada, LucíaPuig, NoemiCedena, Maria TeresaPaiva, BrunoMateos, Maria-VictoriaSan Miguel, Jesus F.Lahuerta, Juan-JoséBladé, JoanTrocóniz, Iñaki FPrognosisMultiple MyelomaNeoplasm, ResidualTreatment OutcomeHumansAntineoplastic Combined Chemotherapy ProtocolsParaproteinsResultado del TratamientoHumanosProtocolos de Quimioterapia Combinada AntineoplásicaPronósticoMieloma MúltipleParaproteínasNeoplasia ResidualResponse kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a "resistance" parameter that reflects the stagnation in the response after an initial descent. Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P = .02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P = .02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.Elsevier20222022-09-0120222022-09-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/18621reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/186212026-06-22T12:44:07Z
dc.title.none.fl_str_mv Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
title Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
spellingShingle Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
Tamariz-Amador, Luis-Esteban
Prognosis
Multiple Myeloma
Neoplasm, Residual
Treatment Outcome
Humans
Antineoplastic Combined Chemotherapy Protocols
Paraproteins
Resultado del Tratamiento
Humanos
Protocolos de Quimioterapia Combinada Antineoplásica
Pronóstico
Mieloma Múltiple
Paraproteínas
Neoplasia Residual
title_short Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
title_full Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
title_fullStr Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
title_full_unstemmed Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
title_sort Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
dc.creator.none.fl_str_mv Tamariz-Amador, Luis-Esteban
Rodriguez-Otero, Paula
Jiménez-Ubieto, Ana
Rosiñol, Laura
Oriol, Albert
Rios, Rafael
Sureda, Anna
Blanchard, María-Jesús
Hernández, Miguel-Teodoro
Cabañas Perianes, Valentin
Jarque, Isidro
Bargay Lleonart, Joan
Gironella, Mercedes
de Arriba, Felipe
Palomera, Luis
Gonzalez-Montes, Yolanda
Martí, Josep M
Krsnik, Isabel
Arguiñano, José María
González, María Esther
Casado, Luis Felipe
González-Rodriguez, Ana Pilar
López-Anglada, Lucía
Puig, Noemi
Cedena, Maria Teresa
Paiva, Bruno
Mateos, Maria-Victoria
San Miguel, Jesus F.
Lahuerta, Juan-José
Bladé, Joan
Trocóniz, Iñaki F
author Tamariz-Amador, Luis-Esteban
author_facet Tamariz-Amador, Luis-Esteban
Rodriguez-Otero, Paula
Jiménez-Ubieto, Ana
Rosiñol, Laura
Oriol, Albert
Rios, Rafael
Sureda, Anna
Blanchard, María-Jesús
Hernández, Miguel-Teodoro
Cabañas Perianes, Valentin
Jarque, Isidro
Bargay Lleonart, Joan
Gironella, Mercedes
de Arriba, Felipe
Palomera, Luis
Gonzalez-Montes, Yolanda
Martí, Josep M
Krsnik, Isabel
Arguiñano, José María
González, María Esther
Casado, Luis Felipe
González-Rodriguez, Ana Pilar
López-Anglada, Lucía
Puig, Noemi
Cedena, Maria Teresa
Paiva, Bruno
Mateos, Maria-Victoria
San Miguel, Jesus F.
Lahuerta, Juan-José
Bladé, Joan
Trocóniz, Iñaki F
author_role author
author2 Rodriguez-Otero, Paula
Jiménez-Ubieto, Ana
Rosiñol, Laura
Oriol, Albert
Rios, Rafael
Sureda, Anna
Blanchard, María-Jesús
Hernández, Miguel-Teodoro
Cabañas Perianes, Valentin
Jarque, Isidro
Bargay Lleonart, Joan
Gironella, Mercedes
de Arriba, Felipe
Palomera, Luis
Gonzalez-Montes, Yolanda
Martí, Josep M
Krsnik, Isabel
Arguiñano, José María
González, María Esther
Casado, Luis Felipe
González-Rodriguez, Ana Pilar
López-Anglada, Lucía
Puig, Noemi
Cedena, Maria Teresa
Paiva, Bruno
Mateos, Maria-Victoria
San Miguel, Jesus F.
Lahuerta, Juan-José
Bladé, Joan
Trocóniz, Iñaki F
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Prognosis
Multiple Myeloma
Neoplasm, Residual
Treatment Outcome
Humans
Antineoplastic Combined Chemotherapy Protocols
Paraproteins
Resultado del Tratamiento
Humanos
Protocolos de Quimioterapia Combinada Antineoplásica
Pronóstico
Mieloma Múltiple
Paraproteínas
Neoplasia Residual
topic Prognosis
Multiple Myeloma
Neoplasm, Residual
Treatment Outcome
Humans
Antineoplastic Combined Chemotherapy Protocols
Paraproteins
Resultado del Tratamiento
Humanos
Protocolos de Quimioterapia Combinada Antineoplásica
Pronóstico
Mieloma Múltiple
Paraproteínas
Neoplasia Residual
description Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a "resistance" parameter that reflects the stagnation in the response after an initial descent. Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P = .02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P = .02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-09-01
2022
2022-09-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/18621
url https://hdl.handle.net/20.500.13003/18621
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419872563232768
score 15,811543

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