%0 Journal Article
%A Mateos, María-Victoria
%A Martínez-López, Joaquin
%A Rodriguez Otero, Paula
%A González-Calle, Verónica
%A Gonzalez, Marta Sonia
%A Oriol, Albert
%A Gutiérrez, Norma C
%A Ríos-Tamayo, Rafael
%A Rosiñol, Laura
%A Alvarez Rivas, Miguel Angel
%A Bargay Lleonart, Joan
%A Gonzalez-Rodriguez, Ana Pilar
%A Alegre, Adrián
%A Escalante, Fernando
%A Iñigo Rodríguez, María Belén
%A de la Rubia, Javier
%A Teruel, Ana Isabel
%A de Arriba, Felipe
%A Palomera, Luis
%A Hernández, Miguel T
%A Lopez Jiménez, Javier
%A Reinoso-Segura, Marta
%A García Mateo, Aránzazu
%A Ocio, Enrique M
%A Paiva, Bruno
%A Puig, Noemi
%A Cedena, Maria Teresa
%A Bladé, Joan
%A Lahuerta, Juan Jose
%A San-Miguel, Jesus F
%T Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance
%D 2024
%U https://hdl.handle.net/20.500.13003/21129
%X 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.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.
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