Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.

Lakhwani, Sunil; Rosiñol, Laura; Puig, Noemí; Pico-Picos, Miguel-Angel; Medina-González, Laura; Martínez-López, Joaquín; Paiva, Bruno; Cedena, Maria Teresa; Oriol, Albert; Rios-Tamayo, Rafael; Blanchard, María-Jesús; Jarque, Isidro; Bargay Lleonart, Joan; Moraleda, José-María; Carrillo-Cruz, Estrella; Sureda, Anna; Krsnik, Isabel; González, Esther; Casado, Luis Felipe; Martí, Josep M; Encinas, Cristina; de Arriba, Felipe; Palomera, Luis; Sampol Mayol, Antonia; González-Montes, Yolanda; Motlló, Cristina; de la Cruz, Javier; Alonso, Rafael; Mateos, Maria-Victoria; Bladé, Joan; Lahuerta, Juan-José; San Miguel, Jesus F.; Hernández, Miguel-Teodoro

Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.

Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from...

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Autores:	Lakhwani, Sunil, Rosiñol, Laura, Puig, Noemí, Pico-Picos, Miguel-Angel, Medina-González, Laura, Martínez-López, Joaquín, Paiva, Bruno, Cedena, Maria Teresa, Oriol, Albert, Rios-Tamayo, Rafael, Blanchard, María-Jesús, Jarque, Isidro, Bargay Lleonart, Joan, Moraleda, José-María, Carrillo-Cruz, Estrella, Sureda, Anna, Krsnik, Isabel, González, Esther, Casado, Luis Felipe, Martí, Josep M, Encinas, Cristina, de Arriba, Felipe, Palomera, Luis, Sampol Mayol, Antonia, González-Montes, Yolanda, Motlló, Cristina, de la Cruz, Javier, Alonso, Rafael, Mateos, Maria-Victoria, Bladé, Joan, Lahuerta, Juan-José, San Miguel, Jesus F., Hernández, Miguel-Teodoro
Tipo de recurso:	artículo
Fecha de publicación:	2024
País:	España
Institución:	Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:	Docusalut
Idioma:	inglés
OAI Identifier:	oai:docusalut.com:20.500.13003/20838
Acceso en línea:	https://hdl.handle.net/20.500.13003/20838
Access Level:	acceso abierto
Palabra clave:	Neoplasm, Residual Aged Hematopoietic Stem Cell Transplantation Adult Humans Antineoplastic Combined Chemotherapy Protocols Middle Aged Immunoglobulin Light Chains Prognosis Multiple Myeloma Male Immunoglobulin Heavy Chains Female Cadenas Pesadas de Inmunoglobulina Mieloma Múltiple Femenino Masculino Cadenas Ligeras de Inmunoglobulina Humanos Persona de Mediana Edad Trasplante de Células Madre Hematopoyéticas Protocolos de Quimioterapia Combinada Antineoplásica Pronóstico Anciano Neoplasia Residual Adulto

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spelling	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.Lakhwani, SunilRosiñol, LauraPuig, NoemíPico-Picos, Miguel-AngelMedina-González, LauraMartínez-López, JoaquínPaiva, BrunoCedena, Maria TeresaOriol, AlbertRios-Tamayo, RafaelBlanchard, María-JesúsJarque, IsidroBargay Lleonart, JoanMoraleda, José-MaríaCarrillo-Cruz, EstrellaSureda, AnnaKrsnik, IsabelGonzález, EstherCasado, Luis FelipeMartí, Josep MEncinas, Cristinade Arriba, FelipePalomera, LuisSampol Mayol, AntoniaGonzález-Montes, YolandaMotlló, Cristinade la Cruz, JavierAlonso, RafaelMateos, Maria-VictoriaBladé, JoanLahuerta, Juan-JoséSan Miguel, Jesus F.Hernández, Miguel-TeodoroNeoplasm, ResidualAgedHematopoietic Stem Cell TransplantationAdultHumansAntineoplastic Combined Chemotherapy ProtocolsMiddle AgedImmunoglobulin Light ChainsPrognosisMultiple MyelomaMaleImmunoglobulin Heavy ChainsFemaleCadenas Pesadas de InmunoglobulinaMieloma MúltipleFemeninoMasculinoCadenas Ligeras de InmunoglobulinaHumanosPersona de Mediana EdadTrasplante de Células Madre HematopoyéticasProtocolos de Quimioterapia Combinada AntineoplásicaPronósticoAncianoNeoplasia ResidualAdultoImmunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with minimal residual disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA /GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next-generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression-free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (95% confidence interval [CI]: 0.21-0.81; P=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (95% CI: -0.04 to 0.14; P<0.001) when adding uHLC IP recovery. Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after 1 year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment (clinicaltrials gov. Identifiers: NCT01916252 and NCT02406144).The Ferrata-Storti Foundation20242024-06-0120242024-06-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/20838reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/208382026-06-22T12:44:07Z
dc.title.none.fl_str_mv	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
title	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
spellingShingle	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection. Lakhwani, Sunil Neoplasm, Residual Aged Hematopoietic Stem Cell Transplantation Adult Humans Antineoplastic Combined Chemotherapy Protocols Middle Aged Immunoglobulin Light Chains Prognosis Multiple Myeloma Male Immunoglobulin Heavy Chains Female Cadenas Pesadas de Inmunoglobulina Mieloma Múltiple Femenino Masculino Cadenas Ligeras de Inmunoglobulina Humanos Persona de Mediana Edad Trasplante de Células Madre Hematopoyéticas Protocolos de Quimioterapia Combinada Antineoplásica Pronóstico Anciano Neoplasia Residual Adulto
title_short	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
title_full	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
title_fullStr	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
title_full_unstemmed	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
title_sort	Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
dc.creator.none.fl_str_mv	Lakhwani, Sunil Rosiñol, Laura Puig, Noemí Pico-Picos, Miguel-Angel Medina-González, Laura Martínez-López, Joaquín Paiva, Bruno Cedena, Maria Teresa Oriol, Albert Rios-Tamayo, Rafael Blanchard, María-Jesús Jarque, Isidro Bargay Lleonart, Joan Moraleda, José-María Carrillo-Cruz, Estrella Sureda, Anna Krsnik, Isabel González, Esther Casado, Luis Felipe Martí, Josep M Encinas, Cristina de Arriba, Felipe Palomera, Luis Sampol Mayol, Antonia González-Montes, Yolanda Motlló, Cristina de la Cruz, Javier Alonso, Rafael Mateos, Maria-Victoria Bladé, Joan Lahuerta, Juan-José San Miguel, Jesus F. Hernández, Miguel-Teodoro
author	Lakhwani, Sunil
author_facet	Lakhwani, Sunil Rosiñol, Laura Puig, Noemí Pico-Picos, Miguel-Angel Medina-González, Laura Martínez-López, Joaquín Paiva, Bruno Cedena, Maria Teresa Oriol, Albert Rios-Tamayo, Rafael Blanchard, María-Jesús Jarque, Isidro Bargay Lleonart, Joan Moraleda, José-María Carrillo-Cruz, Estrella Sureda, Anna Krsnik, Isabel González, Esther Casado, Luis Felipe Martí, Josep M Encinas, Cristina de Arriba, Felipe Palomera, Luis Sampol Mayol, Antonia González-Montes, Yolanda Motlló, Cristina de la Cruz, Javier Alonso, Rafael Mateos, Maria-Victoria Bladé, Joan Lahuerta, Juan-José San Miguel, Jesus F. Hernández, Miguel-Teodoro
author_role	author
author2	Rosiñol, Laura Puig, Noemí Pico-Picos, Miguel-Angel Medina-González, Laura Martínez-López, Joaquín Paiva, Bruno Cedena, Maria Teresa Oriol, Albert Rios-Tamayo, Rafael Blanchard, María-Jesús Jarque, Isidro Bargay Lleonart, Joan Moraleda, José-María Carrillo-Cruz, Estrella Sureda, Anna Krsnik, Isabel González, Esther Casado, Luis Felipe Martí, Josep M Encinas, Cristina de Arriba, Felipe Palomera, Luis Sampol Mayol, Antonia González-Montes, Yolanda Motlló, Cristina de la Cruz, Javier Alonso, Rafael Mateos, Maria-Victoria Bladé, Joan Lahuerta, Juan-José San Miguel, Jesus F. Hernández, Miguel-Teodoro
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 author author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv	Neoplasm, Residual Aged Hematopoietic Stem Cell Transplantation Adult Humans Antineoplastic Combined Chemotherapy Protocols Middle Aged Immunoglobulin Light Chains Prognosis Multiple Myeloma Male Immunoglobulin Heavy Chains Female Cadenas Pesadas de Inmunoglobulina Mieloma Múltiple Femenino Masculino Cadenas Ligeras de Inmunoglobulina Humanos Persona de Mediana Edad Trasplante de Células Madre Hematopoyéticas Protocolos de Quimioterapia Combinada Antineoplásica Pronóstico Anciano Neoplasia Residual Adulto
topic	Neoplasm, Residual Aged Hematopoietic Stem Cell Transplantation Adult Humans Antineoplastic Combined Chemotherapy Protocols Middle Aged Immunoglobulin Light Chains Prognosis Multiple Myeloma Male Immunoglobulin Heavy Chains Female Cadenas Pesadas de Inmunoglobulina Mieloma Múltiple Femenino Masculino Cadenas Ligeras de Inmunoglobulina Humanos Persona de Mediana Edad Trasplante de Células Madre Hematopoyéticas Protocolos de Quimioterapia Combinada Antineoplásica Pronóstico Anciano Neoplasia Residual Adulto
description	Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with minimal residual disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA /GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next-generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression-free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (95% confidence interval [CI]: 0.21-0.81; P=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (95% CI: -0.04 to 0.14; P<0.001) when adding uHLC IP recovery. Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after 1 year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment (clinicaltrials gov. Identifiers: NCT01916252 and NCT02406144).
publishDate	2024
dc.date.none.fl_str_mv	2024 2024-06-01 2024 2024-06-01
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/20.500.13003/20838
url	https://hdl.handle.net/20.500.13003/20838
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 Atribución-NoComercial 4.0 Internacional http://creativecommons.org/licenses/by-nc/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 Atribución-NoComercial 4.0 Internacional http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	The Ferrata-Storti Foundation
publisher.none.fl_str_mv	The Ferrata-Storti Foundation
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
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Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.

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