Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial
Abstract Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd wi...
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Format: | Article |
Language: | English |
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Nature Publishing Group
2021-05-01
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Series: | Blood Cancer Journal |
Online Access: | https://doi.org/10.1038/s41408-021-00490-8 |
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English |
format |
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DOAJ |
author |
Noemi Puig Miguel T. Hernández Laura Rosiñol Esther González Felipe de Arriba Albert Oriol Verónica González-Calle Fernando Escalante Javier de la Rubia Mercedes Gironella Rafael Ríos Ricarda García-Sánchez José M. Arguiñano Adrián Alegre Jesús Martín Norma. C. Gutiérrez María J. Calasanz María L. Martín María del Carmen Couto María Casanova Mario Arnao Ernesto Pérez-Persona Sebastián Garzón Marta S. González Guillermo Martín-Sánchez Enrique M. Ocio Morton Coleman Cristina Encinas Ana M. Vale Ana I. Teruel María Cortés-Rodríguez Bruno Paiva M. Teresa Cedena Jesús F. San-Miguel Juan J. Lahuerta Joan Bladé Ruben Niesvizky María-Victoria Mateos |
spellingShingle |
Noemi Puig Miguel T. Hernández Laura Rosiñol Esther González Felipe de Arriba Albert Oriol Verónica González-Calle Fernando Escalante Javier de la Rubia Mercedes Gironella Rafael Ríos Ricarda García-Sánchez José M. Arguiñano Adrián Alegre Jesús Martín Norma. C. Gutiérrez María J. Calasanz María L. Martín María del Carmen Couto María Casanova Mario Arnao Ernesto Pérez-Persona Sebastián Garzón Marta S. González Guillermo Martín-Sánchez Enrique M. Ocio Morton Coleman Cristina Encinas Ana M. Vale Ana I. Teruel María Cortés-Rodríguez Bruno Paiva M. Teresa Cedena Jesús F. San-Miguel Juan J. Lahuerta Joan Bladé Ruben Niesvizky María-Victoria Mateos Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial Blood Cancer Journal |
author_facet |
Noemi Puig Miguel T. Hernández Laura Rosiñol Esther González Felipe de Arriba Albert Oriol Verónica González-Calle Fernando Escalante Javier de la Rubia Mercedes Gironella Rafael Ríos Ricarda García-Sánchez José M. Arguiñano Adrián Alegre Jesús Martín Norma. C. Gutiérrez María J. Calasanz María L. Martín María del Carmen Couto María Casanova Mario Arnao Ernesto Pérez-Persona Sebastián Garzón Marta S. González Guillermo Martín-Sánchez Enrique M. Ocio Morton Coleman Cristina Encinas Ana M. Vale Ana I. Teruel María Cortés-Rodríguez Bruno Paiva M. Teresa Cedena Jesús F. San-Miguel Juan J. Lahuerta Joan Bladé Ruben Niesvizky María-Victoria Mateos |
author_sort |
Noemi Puig |
title |
Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial |
title_short |
Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial |
title_full |
Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial |
title_fullStr |
Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial |
title_full_unstemmed |
Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial |
title_sort |
lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial |
publisher |
Nature Publishing Group |
series |
Blood Cancer Journal |
issn |
2044-5385 |
publishDate |
2021-05-01 |
description |
Abstract Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene. |
url |
https://doi.org/10.1038/s41408-021-00490-8 |
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doaj-fb9a610fa208459ba3fc58d65716e2202021-05-23T11:11:54ZengNature Publishing GroupBlood Cancer Journal2044-53852021-05-0111511110.1038/s41408-021-00490-8Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trialNoemi Puig0Miguel T. Hernández1Laura Rosiñol2Esther González3Felipe de Arriba4Albert Oriol5Verónica González-Calle6Fernando Escalante7Javier de la Rubia8Mercedes Gironella9Rafael Ríos10Ricarda García-Sánchez11José M. Arguiñano12Adrián Alegre13Jesús Martín14Norma. C. Gutiérrez15María J. Calasanz16María L. Martín17María del Carmen Couto18María Casanova19Mario Arnao20Ernesto Pérez-Persona21Sebastián Garzón22Marta S. González23Guillermo Martín-Sánchez24Enrique M. Ocio25Morton Coleman26Cristina Encinas27Ana M. Vale28Ana I. Teruel29María Cortés-Rodríguez30Bruno Paiva31M. Teresa Cedena32Jesús F. San-Miguel33Juan J. Lahuerta34Joan Bladé35Ruben Niesvizky36María-Victoria Mateos37Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONCHospital Universitario de CanariasHematology Department, Hospital Clinic, IDIBAPSHospital Universitario de CabueñesHospital Morales Meseguer, IMIB-Arrixaca, Universidad de MurciaInstitut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i PujolHematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONCHospital Universitario de LeónHematology Department, Catholic University of Valencia and Hospital Doctor PesetHospital Univeristari Vall d´HebronHospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria IBS GRANADAHospital Universitario Virgen de la VictoriaComplejo Hospitalario de NavarraHospital Universitario de La PrincesaHospital Universitario Virgen del RocíoHematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONCClínica Universidad de Navarra, CIMA, CIBERONC, IDISNAHospital Universitario 12 de Octubre, CIBERONC, Instituto de InvestigaciónHospital Universitario Virgen de ValmeHematology Department, Hospital Costa del Sol de MarbellaHematology Department, Hospital Universitario y Politécnico La FeBioaraba Health Research Institute, Oncohematology Research Group; Osakidetza, Álava University Hospital, Hematology DepartmentHospital del SAS de JerezHospital Universitario de SantiagoHematology Department, Hospital Universitario Marqués de ValdecillaHematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONCDivision of Hematology and Oncology, Weill Cornell MedicineHospital Universitario Gregorio MarañónCHUACHospital Clínico Universitario de ValenciaHematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONCClínica Universidad de Navarra, CIMA, CIBERONC, IDISNAHospital Universitario 12 de Octubre, CIBERONC, Instituto de InvestigaciónClínica Universidad de Navarra, CIMA, CIBERONC, IDISNAInstituto de Investigación del Hospital UniversitarioHematology Department, Hospital Clinic, IDIBAPSDivision of Hematology and Oncology, Weill Cornell MedicineHematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONCAbstract Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.https://doi.org/10.1038/s41408-021-00490-8 |