Scientific publications
Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance. Scientific Publication
María-Victoria Mateos 1 , Joaquin Martínez-López 2 , Paula Rodriguez Otero 3 , Verónica González-Calle 4 5 , Marta Sonia Gonzalez 6 , Albert Oriol 7 , Norma C Gutiérrez 8 9 10 , Rafael Ríos-Tamayo 11 , Laura Rosiñol 12 , Miguel Angel Alvarez Rivas 13 , Joan Bargay 14 , Ana Pilar Gonzalez-Rodriguez 15 , Adrián Alegre 16 , Fernando Escalante 17 , María Belén Iñigo Rodríguez 18 , Javier De La Rubia 19 20 21 , Ana Isabel Teruel 22 , Felipe de Arriba 23 , Luis Palomera 24 , Miguel T Hernández 25 , Javier Lopez Jiménez 26 , Marta Reinoso-Segura 27 , Aránzazu García Mateo 28 , Enrique M Ocio 29 , Bruno Paiva 30 , Noemi Puig 31 , M Teresa Cedena 32 , Joan Bladé 33 , Juan Jose Lahuerta 34 , Jesus F San-Miguel 35 ; Spanish Myeloma Group (GEM-Pethema)
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 = .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.
CITATION J Clin Oncol. 2024 Sep 20;42(27):3247-3256. doi: 10.1200/JCO.23.02771. Epub 2024 Jul 22
Our authors
