Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group

This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty-seven RRMM patients with a median of three prior lines (2-8) and 94% refractory to lenalidomide wer...

Descripción completa

Detalles Bibliográficos
Autores: Ocio EM, Motlló C, Rodríguez-Otero P, Martínez-López J, Cejalvo MJ, Martín-Sánchez J, Bladé J, García-Malo MD, Dourdil MV, García-Mateo A, de Arriba F, García-Sanz R, de la Rubia J, Oriol A, Lahuerta JJ, San-Miguel JF, Mateos MV
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p7482
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/7482
Access Level:acceso abierto
Palabra clave:filanesib
KSP
myeloma
Pomalidomide
AAG
id ES_92b17d93874a4eacb215dfd12ebc6cde
oai_identifier_str oai:fisabio.fundanetsuite.com:p7482
network_acronym_str ES
network_name_str España
repository_id_str
spelling Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM groupOcio EMMotlló CRodríguez-Otero PMartínez-López JCejalvo MJMartín-Sánchez JBladé JGarcía-Malo MDDourdil MVGarcía-Mateo Ade Arriba FGarcía-Sanz Rde la Rubia JOriol ALahuerta JJSan-Miguel JFMateos MVfilanesibKSPmyelomaPomalidomideAAGThis phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty-seven RRMM patients with a median of three prior lines (2-8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1 center dot 25 mg/m(2) of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1-21 and dexamethasone 40 mg weekly. The defined threshold for success was achieved, with 18 out of 31 patients obtaining at least minor response (MR) in the phase II. In the global population, 51% of patients achieved at least partial response (PR) and 60% >= MR, resulting in a median progression-free survival (mPFS) of seven months and overall survival (OS) of 19 months. The main toxicity was haematological. Importantly, patients with low serum levels of alpha 1-acid glycoprotein (AAG) at baseline (<800 mg/l) had a superior response (overall response rate of 62% vs. 17%; P = 0 center dot 04), which also translated into a longer mPFS (9 vs. 2 months; P = 0 center dot 014). In summary, filanesib with pomalidomide and dexamethasone is active in RRMM although with significant haematological toxicity. Most importantly, high levels of AAG can identify patients unlikely to respond to this strategy.WILEY2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/7482BRITISH JOURNAL OF HAEMATOLOGYISSN: 00071048ISSNe: 13652141reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p74822026-06-11T12:45:17Z
dc.title.none.fl_str_mv Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
title Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
spellingShingle Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
Ocio EM
filanesib
KSP
myeloma
Pomalidomide
AAG
title_short Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
title_full Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
title_fullStr Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
title_full_unstemmed Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
title_sort Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
dc.creator.none.fl_str_mv Ocio EM
Motlló C
Rodríguez-Otero P
Martínez-López J
Cejalvo MJ
Martín-Sánchez J
Bladé J
García-Malo MD
Dourdil MV
García-Mateo A
de Arriba F
García-Sanz R
de la Rubia J
Oriol A
Lahuerta JJ
San-Miguel JF
Mateos MV
author Ocio EM
author_facet Ocio EM
Motlló C
Rodríguez-Otero P
Martínez-López J
Cejalvo MJ
Martín-Sánchez J
Bladé J
García-Malo MD
Dourdil MV
García-Mateo A
de Arriba F
García-Sanz R
de la Rubia J
Oriol A
Lahuerta JJ
San-Miguel JF
Mateos MV
author_role author
author2 Motlló C
Rodríguez-Otero P
Martínez-López J
Cejalvo MJ
Martín-Sánchez J
Bladé J
García-Malo MD
Dourdil MV
García-Mateo A
de Arriba F
García-Sanz R
de la Rubia J
Oriol A
Lahuerta JJ
San-Miguel JF
Mateos MV
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv filanesib
KSP
myeloma
Pomalidomide
AAG
topic filanesib
KSP
myeloma
Pomalidomide
AAG
description This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty-seven RRMM patients with a median of three prior lines (2-8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1 center dot 25 mg/m(2) of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1-21 and dexamethasone 40 mg weekly. The defined threshold for success was achieved, with 18 out of 31 patients obtaining at least minor response (MR) in the phase II. In the global population, 51% of patients achieved at least partial response (PR) and 60% >= MR, resulting in a median progression-free survival (mPFS) of seven months and overall survival (OS) of 19 months. The main toxicity was haematological. Importantly, patients with low serum levels of alpha 1-acid glycoprotein (AAG) at baseline (<800 mg/l) had a superior response (overall response rate of 62% vs. 17%; P = 0 center dot 04), which also translated into a longer mPFS (9 vs. 2 months; P = 0 center dot 014). In summary, filanesib with pomalidomide and dexamethasone is active in RRMM although with significant haematological toxicity. Most importantly, high levels of AAG can identify patients unlikely to respond to this strategy.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/7482
url https://fisabio.portalinvestigacion.com/publicaciones/7482
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv BRITISH JOURNAL OF HAEMATOLOGY
ISSN: 00071048
ISSNe: 13652141
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869413491653214208
score 15,811543

Similares en LA Referencia