Mateos, María-VictoriaMartínez-López, JoaquinRodriguez Otero, PaulaGonzález-Calle, VerónicaGonzalez, Marta SoniaOriol, AlbertGutiérrez, Norma CRíos-Tamayo, RafaelRosiñol, LauraAlvarez Rivas, Miguel AngelBargay Lleonart, JoanGonzalez-Rodriguez, Ana PilarAlegre, AdriánEscalante, FernandoIñigo Rodríguez, María Belénde la Rubia, JavierTeruel, Ana Isabelde Arriba, FelipePalomera, LuisHernández, Miguel TLopez Jiménez, JavierReinoso-Segura, MartaGarcía Mateo, AránzazuOcio, Enrique MPaiva, BrunoPuig, NoemiCedena, Maria TeresaBladé, JoanLahuerta, Juan JoseSan-Miguel, Jesus F2024-10-182024-10-182024-09-20Mateos MV, Martínez-López J, Rodriguez Otero P, González-Calle V, Gonzalez MS, Oriol A, et al. Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance. J Clin Oncol. 2024 Sep 20;42(27):3247–56.https://hdl.handle.net/20.500.13003/21129Early 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. 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. 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 = .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. 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Disease ProgressionAgedHematopoietic Stem Cell TransplantationAdultTransplantation, AutologousHumansMelphalanAntineoplastic Combined Chemotherapy ProtocolsSmoldering Multiple MyelomaMiddle AgedOligopeptidesConsolidation ChemotherapyLenalidomideMaleMultiple MyelomaMaintenance ChemotherapyFemaleDexamethasoneresearch articleLenalidomidaMieloma Múltiple QuiescenteDexametasonaMieloma MúltipleFemeninoQuimioterapia de ConsolidaciónQuimioterapia de MantenciónMasculinoOligopéptidosHumanosPersona de Mediana EdadTrasplante de Células Madre HematopoyéticasProtocolos de Quimioterapia Combinada AntineoplásicaMelfalánAncianoProgresión de la EnfermedadTrasplante AutólogoAdultoLenalidomideDexamethasoneOligopeptidesAntineoplastic Combined Chemotherapy ProtocolsSmoldering Multiple MyelomaHumansMaleFemaleMiddle AgedAgedAdultHematopoietic Stem Cell TransplantationTransplantation, AutologousMelphalanConsolidation ChemotherapyMaintenance ChemotherapyMultiple MyelomaDisease Progression10.1200/JCO.23.027711527-775539038268L20339840672-s2.0-85201052109001313264500010open access