Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial
Noemí 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-María Arguiñano, Adrían Alegre, Jesús Martín, Norma C. Gutiérrez, Marı́a José Calasanz, María Luisa Martín, María del Carmen Couto, María Casanova, Mario Arnao, Ernesto Pérez Persona, Sebastián Garzón, Marta Sonia González, Guillermo Martín-Sánchez, Enrique M. Ocio, Morton Coleman, Cristina Encinas, Ana Vale, Ana Isabel Teruel, María Cortés Rodríguez, Bruno Paiva, María‐Teresa Cedena, Jesús F. San Miguel, Juan José Lahuerta, Joan Bladé, Rubén Niesvizky, María‐Victoria Mateos
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.