Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant : a randomized trial
Puig, Noemi (Hospital Universitario de Salamanca)
Hernández, Miguel Teodoro (Hospital Universitario de Canarias (La Laguna))
Rosiñol, Laura (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
González, Esther (Hospital Universitario de Cabueñes (Gijón))
De Arriba, Felipe (Instituto Murciano de Investigación Biosanitaria)
Oriol, Albert (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
González-Calle, Verónica (Hospital Universitario de Salamanca)
Escalante, Fernando (Hospital Universitario de León)
de la Rubia, Javier (Hospital Universitari Doctor Peset (València))
Gironella, Mercedes (Hospital Universitari Vall d'Hebron)
Ríos-Tamayo, Rafael (Instituto de Investigación Sanitaria de Granada)
García-Sánchez, Ricarda (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Arguiñano, José M (Complejo Hospitalario de Navarra)
Alegre, Adrian (Hospital Universitario de la Princesa (Madrid))
Martín Sánchez, Jesús (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Gutiérrez, Norma C. (Hospital Universitario de Salamanca)
Calasanz, M.J (Clínica Universidad de Navarra)
Martín, María L. (Hospital Universitario 12 de Octubre (Madrid))
Couto, María del Carmen (Hospital Universitario Virgen de Valme (Sevilla, Andalusia))
Casanova, María (Hematology Department. Hospital Costa del Sol de Marbella)
Arnao, Mario (Hospital Universitari i Politècnic La Fe (València))
Pérez-Persona, Ernesto (Instituto de Investigación Sanitaria Bioaraba (Vitoria, País Basc))
Garzón, Sebastián (Hospital del SAS de Jerez)
González, Marta S. (Hospital Universitario de Santiago)
Martín-Sánchez, Guillermo (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Ocio, Enrique M. (Hospital Universitario de Salamanca)
Coleman, Morton (Division of Hematology and Oncology. Weill Cornell Medicine)
Encinas, Cristina (Hospital General Universitario Gregorio Marañón)
Vale, Ana M. (CHUAC)
Teruel, Ana I. (Hospital Clínic Universitari (València))
Cortés-Rodríguez, María (Hospital Universitario de Salamanca)
Paiva, Bruno (Clínica Universidad de Navarra)
Cedena, María Teresa (Hospital Universitario 12 de Octubre (Madrid))
San-Miguel, J (Clínica Universidad de Navarra)
Lahuerta, J. J (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Bladé Creixenti, Juan (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Niesvizky, Ruben (Division of Hematology and Oncology. Weill Cornell Medicine)
Mateos, M. V (Hospital Universitario de Salamanca)

Date:	2021
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; Clarithromycin ; Dexamethasone ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lenalidomide ; Male ; Multiple Myeloma ; Transplantation, Autologous ; Treatment Outcome
Published in:	Blood Cancer Journal, Vol. 11 Núm. 5 (may 2021) , art. 101, ISSN 2044-5385

DOI: 10.1038/s41408-021-00490-8
PMID: 34021118

11 p, 1.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles