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, Otero, PR, González-Calle, V, Gonzalez, MS, Oriol, A, Gutiérrez, NC, Rios-Tamayo, R, Rosiñol, L, Rivas, MAA, Bargay, J, Gonzalez-Rodriguez, AP, Alegre, A, Escalante, F, Rodriguez, MBI, de la Rubia, J, Teruel, AI, de Arriba, F, Palomera, L, Hernández, MT, Jiménez, JL, Reinoso-Segura, M, Mateo, AG, Ocio, EM, Paiva, B, Puig, N, Cedena, MT, Blade, J, Lahuerta, JJ and San-Miguel, JF
Publicada:
20 sep 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:
Hosp Univ Salamanca, IBSAL, Ctr Invest Canc IBMCC USAL CSIC, Salamanca, Spain
Martínez-López, J:
Univ Complutense, Sch Med, Hosp Univ Octubre 12, Dept Dermatol,Inst I 12, Madrid, Spain
Otero, PR:
IDISNA, Canc Ctr Clin Univ Navarra CCUN, CIMA, CIBERONC, Pamplona, Spain
González-Calle, V:
Hosp Univ Salamanca, Hematol Dept, IBSAL, CIBERONC, Salamanca, Spain
Ctr Invest Canc IBMCC USAL CSIC, Salamanca, Spain
Gonzalez, MS:
Hosp Clin Univ Santiago Compostela, Hematol Dept, Santiago De Compostela, Spain
:
Hosp Germans Trias i Pujol, Josep Carreras Res Inst, Inst Catala Oncol, Hematol Dept, Badalona, Spain
Gutiérrez, NC:
Univ Hosp Salamanca, Inst Biomed Res Salamanca, Dept Hematol, Salamanca, Spain
CSIC USAL, Canc Res Ctr IBMCC, Salamanca, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Rios-Tamayo, R:
Hosp Univ Puerta Hierro Majadahonda, Majadahonda, Spain
Rosiñol, L:
Hosp Clin Barcelona, ICMHO, Hematol Dept, Barcelona, Spain
Rivas, MAA:
Hosp Univ Reina Sofia, Serv Hematol & Hemoterapia, Cordoba, Spain
Bargay, J:
Hosp Univ Son Llatzer, Fdn Inst Invest Sanitaria Illes Balears IdISBa, Endocrinol & Nutr Dept, Palma de Mallorca, Spain
Gonzalez-Rodriguez, AP:
Hosp Univ Cent Asturias, Hematol Dept, Oviedo, Spain
Alegre, A:
Univ Hosp Quironsalud, Hematol Dept, Madrid, Spain
Escalante, F:
Complejo Asistencial Univ Leon, Serv Hematol, Leon, Spain
Rodriguez, MBI:
Hosp Clin San Carlos, Dept Hematol, Madrid, Spain
de la Rubia, J:
Hosp Univ & Politecn La Fe, Hematol Dept, Valencia, Spain
Univ Catol Valencia, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Teruel, AI:
Hosp Clin Univ Valencia, Hematol Dept, Valencia, Spain
de Arriba, F:
Univ Murcia, Hosp Univ Morales Meseguer, Ctr Reg Hemodonac, Hematol Dept,IMIB Pascual Parrilla, Murcia, Spain
Palomera, L:
Hosp Clin Univ Lozano Blesa, Inst Invest Sanitaria Aragon, Zaragoza, Spain
Hernández, MT:
Hosp Univ Canarias, Immunol Dept, Santa Cruz De Tenerife, Spain
Jiménez, JL:
Hosp Ramon & Cajal, Dept Hematol, Madrid, Spain
Reinoso-Segura, M:
Univ Seville, Univ Hosp Virgen Rocio, Dept Hematol, Inst Biomed Sevilla IBIS CSIC CIBERONC, Seville 41013, Spain
Mateo, AG:
Complejo Asistencial Segovia, Segovia, Spain
Ocio, EM:
Univ Cantabria, Hosp Univ Marques de Valdecilla, IDIVAL, Dept Pathol, Santander, Spain
Paiva, B:
Clin Univ Navarra, Dept Hematol, Pamplona, Spain
Puig, N:
Hosp Univ Salamanca HUSAL, IBSAL, IBMCC USAL CSIC, CIBERONC, Salamanca, Spain
Cedena, MT:
Hosp Univ 12 Octubre, Inst Invest i 12, Madrid, Spain
Blade, J:
Hosp Clin Barcelona, ICMHO, Hematol Dept, Barcelona, Spain
Lahuerta, JJ:
Hosp Univ 12 Octubre, Inst Invest, Dept Rheumatol, Madrid, Spain
San-Miguel, JF:
IDISNA, Canc Ctr Clin Univ Navarra CCUN, CIMA, CIBERONC, Pamplona, Spain
Green Published
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