Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance
Por:
Mateos MV, Martínez-López J, Rodriguez Otero P, González-Calle V, Gonzalez MS, Oriol A, Gutiérrez NC, Ríos-Tamayo R, Rosiñol L, Alvarez Rivas MA, Bargay J, Gonzalez-Rodriguez AP, Alegre A, Escalante F, Iñigo Rodríguez MB, De La Rubia J, Teruel AI, de Arriba F, Palomera L, Hernández MT, Lopez Jiménez J, Reinoso-Segura M, García Mateo A, Ocio EM, Paiva B, Puig N, Cedena MT, Bladé J, Lahuerta JJ, San-Miguel JF
Publicada:
20 sep 2024
Ahead of Print:
22 jul 2024
Resumen:
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.
Filiaciones:
Mateos MV:
Hematology Department, Hospital Universitario de Salamanca-IBSAL, CIBERONC and Centro de Investigación del Cáncer, IBMCC (USAL-CSIC), Salamanca, Spain
Martínez-López J:
Hematology Department, Hospital 12 de Octubre, Medicine Department, Medicine School of Complutense University, I+12. CNIO, Madrid, Spain
Rodriguez Otero P:
Hematology Department, Cancer Center Clinica Universidad de Navarra (CCUN), Cima, CIBERONC, Pamplona, Spain
González-Calle V:
Hematology Department, Hospital Universitario de Salamanca-IBSAL, CIBERONC, Salamanca, Spain
Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain
Gonzalez MS:
Hematology Department, Hospital Clinico Universitario Santiago de Compostela, Santiago de Compostela, Spain
Oriol A:
Clinical Hematology, Institut Català d'Oncologia and Josep Carreras Research Institute, Hospital Germans Trias I Pujol, Badalona, Spain
Gutiérrez NC:
Hematology Department, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
Ríos-Tamayo R:
Unidad de Gammapatías Monoclonales, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
Rosiñol L:
Hematology Department, Hospital Clínic, Barcelona, Spain
Alvarez Rivas MA:
Servicio de Hematología y Hemoterapia, Hospital Universitario Reina Sofía, Córdoba, Spain
Bargay J:
Hematology Department, Hospital Universitario Son Llatzer, IdISBa (Institut d'Investigació Sanitaria Illes Balears), Palma, Spain
Gonzalez-Rodriguez AP:
Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
Alegre A:
Hematology Department, University Hospital La Princesa & University Hospital QuironSalud, Autonoma-University, Madrid, Spain
Escalante F:
Servicio de Hematología, Unidad i+i, Complejo Asistencial Universitario de León, León, Spain
Iñigo Rodríguez MB:
Hematology Department, Hospital Clínico San Carlos, Madrid, Spain
De La Rubia J:
Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Universidad Católica de Valencia, Valencia, Spain
Centro de Investigación Biomédica en Red de Cáncer, CIBERONC CB16/12/00284, Instituto de Salud Carlos III, Madrid, Spain
Teruel AI:
Hematology Department, Hospital Clinico Universitario de Valencia, Valencia, Spain
de Arriba F:
Servicio de Hematologia, Hospital Universitario Morales Meseguer, IMIB-Pascual Parrilla, Universidad de Murcia, Murcia, Spain
Palomera L:
Hematology Department, Hospital Clínico Universitario Lozano Blesa, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
Hernández MT:
Hematology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
Lopez Jiménez J:
Hematology Department, Hospital Ramón y Cajal, Madrid, Spain
Reinoso-Segura M:
Hematology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Universidad de Sevilla, Sevilla, Spain
García Mateo A:
Hematology Department, Complejo Asistencial de Segovia, Segovia, Spain
Ocio EM:
Hematology Department, Hospital Universitario Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain
Paiva B:
Hematology Department, Clinica Universidad de Navarra, Pamplona, Spain
Puig N:
Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain
Cedena MT:
Hematology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación i+12, Madrid, Spain
Bladé J:
Hematology Department, Hospital Clinic, IDIBARS, Barcelona, Spain
Lahuerta JJ:
Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain
San-Miguel JF:
Cancer Center Clinica Universidad de Navarra (CCUN), CIMA, IDISNA, CIBERONC, Pamplona, Spain
Green Published
|