Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance

• Published in: Journal of clinical oncology Vol. 42; no. 27; pp. JCO2302771 - 3256
• Main Authors: Mateos, María-Victoria, Martínez-López, Joaquin, Rodriguez Otero, Paula, González-Calle, Verónica, Gonzalez, Marta Sonia, Oriol, Albert, Gutiérrez, Norma C, Ríos-Tamayo, Rafael, Rosiñol, Laura, Alvarez Rivas, Miguel Angel, Bargay, Joan, Gonzalez-Rodriguez, Ana Pilar, Alegre, Adrián, Escalante, Fernando, Iñigo Rodríguez, María Belén, De La Rubia, Javier, Teruel, Ana Isabel, de Arriba, Felipe, Palomera, Luis, Hernández, Miguel T, Lopez Jiménez, Javier, Reinoso-Segura, Marta, García Mateo, Aránzazu, Ocio, Enrique M, Paiva, Bruno, Puig, Noemi, Cedena, M Teresa, Bladé, Joan, Lahuerta, Juan Jose, San-Miguel, Jesus F
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 20.09.2024
• Subjects: ORIGINAL REPORTS
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.23.02771

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/m ) 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; = .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.