1. Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial
- Author
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María Cortés-Rodríguez, Norma C. Gutiérrez, Juan J. Lahuerta, María del Carmen Couto, Enrique M. Ocio, Jose M Arguiñano, Jesús F. San-Miguel, María José Casanova, Jesús Martín, M. Teresa Cedena, Javier de la Rubia, Maria Luisa Martin, Ana Isabel Teruel, Esther González, Bruno Paiva, Ernesto Pérez-Persona, Verónica González-Calle, Laura Rosiñol, María José Calasanz, Cristina Encinas, Rafael Rios, Morton Coleman, Ruben Niesvizky, Miguel T. Hernandez, Ana M. Vale, Maria-Victoria Mateos, Adrian Alegre, Mercedes Gironella, Noemi Puig, Sebastián Garzón, Ricarda García-Sánchez, Felipe de Arriba, Guillermo Martín-Sánchez, Joan Bladé, Mario Arnao, Marta González, Fernando Escalante, Albert Oriol, Universidad de Cantabria, Institut Català de la Salut, [Puig N] Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain. [Hernández MT] Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain. [Rosiñol L] Hematology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain. [González E] Hospital Universitario de Cabueñes, Gijón, Spain. [de Arriba F] Hospital Morales Meseguer, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain. [Oriol A] Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain. [Gironella M] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Male ,Surgical Procedures, Operative::Transplantation::Transplantation, Autologous [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Myeloma ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Gastroenterology ,THERAPY ,Dexamethasone ,law.invention ,Randomized controlled trial ,law ,Clarithromycin ,Antineoplastic Combined Chemotherapy Protocols ,terapéutica::farmacoterapia::farmacoterapia combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Clinical endpoint ,Lenalidomide ,Multiple myeloma ,RC254-282 ,Aged, 80 and over ,POMALIDOMIDE ,Therapeutics::Drug Therapy::Drug Therapy, Combination [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Hematopoietic Stem Cell Transplantation ,Neoplasms::Neoplasms by Histologic Type::Neoplasms, Plasma Cell::Multiple Myeloma [DISEASES] ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Hematology ,Treatment Outcome ,Oncology ,BIRD ,BIAXIN ,Randomized controlled trials ,Female ,Multiple Myeloma ,medicine.drug ,Mieloma múltiple - Tractament ,medicine.medical_specialty ,LOW-DOSE DEXAMETHASONE ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Neutropenia ,Transplantation, Autologous ,Article ,Internal medicine ,medicine ,neoplasias::neoplasias por tipo histológico::neoplasias de células plasmáticas::mieloma múltiple [ENFERMEDADES] ,Humans ,Adverse effect ,COMBINATION ,intervenciones quirúrgicas::trasplante::trasplante autólogo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Aged ,business.industry ,Teràpia cel·lular ,medicine.disease ,business - Abstract
© The Author(s) 2021., 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.
- Published
- 2021