@article{10902/34440,
year = {2024},
url = {https://hdl.handle.net/10902/34440},
abstract = {Purpose: Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM. 
Methods: Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m2 ) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years. The primary end point was undetectable measurable residual disease (uMRD) rate by next-generation flow after ASCT. Sustained uMRD 4 years after ASCT was the secondary end point. 
Results: Between June 2015 and June 2017, 90 patients were included, and 31% met at least one SixtyLightchain MRI (SLiM)-hypercalcemia, renal impairment, anemia, bone disease (CRAB) criterion. After a median follow-up of 70.1 months, 3 months after ASCT, in the intention-to-treat population, 56 (62%) of 90 patients had uMRD, and 4 years later, it was sustained in 29 patients (31%). Five patients progressed to MM, and the 70-month progression rate was 94% (95% CI, 84 to 89). The presence of any SLiM CRAB criteria predicted progression to MM (four of the five patients; hazard ratio, 0.12; 95% CI, 0.14 to 1.13; P 5 .03). Thirty-six patients showed biochemical progression, and failure to achieve uMRD at the end of treatment predicted it. The 70-month overall survival was 92% (95% CI, 82 to 89). Neutropenia and infections were the most frequent adverse events during treatment, resulting in one treatment related death. Three second primary malignancies have been reported. 
Conclusion: Although a longer follow-up is needed, this curative approach is encouraging and more effective than active MM, with 31% of the patients maintaining the uMRD 4 years after HDM-ASCT.},
organization = {SUPPORT: Supported by the Pethema Foundation. The manufacturers of carfilzomib (Amgen) and lenalidomide (Celgene BMS, Summit, NJ, USA) supplied the drugs at no charge and provided financial support, but were not involved in the analysis, interpretation, or decision to publish the trial. This study was also supported by the Instituto de Salud Carlos III/ Subdireccion General de Investigación Sanitaria, Spain (FIS: PI21/ 01917; PI21/01751; PI21/01816).},
publisher = {American Society of Clinical Oncology by Lippincott Williams & Wilkins with the assistance of Stanford University's HighWire Press},
publisher = {Journal of Clinical Oncology, 2024, 42(27), 3247-3260},
title = {Curative strategy for high-risk smoldering myeloma: carfilzomib, lenalidomide, and dexamethasone (KRd) followed by transplant, KRd consolidation, and Rd maintenance},
author = {Mateos, María-Victoria and Martínez-López, Joaquín and Rodríguez Otero, Paula and González-Calle, Verónica and González, Marta Sonia and Oriol, Albert and Gutiérrez, Norma C. and Ríos-Tamayo, Rafael and Rosiñol, Laura and Álvarez Rivas, Miguel Ángel and Bargay, Joan and González-Rodríguez, Ana Pilar and Alegre, Adrián and Escalante, Fernando and Íñigo Rodríguez, María Belén and De La Rubia, Javier and Teruel, Ana Isabel and Arriba, Felipe de and Ocio San Miguel, Enrique María},
}