Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance-Reference-Cited by-同舟云学术

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

Published:2024-07-22 Issue: Volume: Page:
ISSN:0732-183X
Container-title:Journal of Clinical Oncology
language:en
Short-container-title:JCO

Author:

Mateos María-Victoria¹^ORCID,Martínez-López Joaquin²^ORCID,Rodriguez Otero Paula³^ORCID,González-Calle Verónica⁴⁵,Gonzalez Marta Sonia⁶,Oriol Albert⁷^ORCID,Gutiérrez Norma C.⁸⁹¹⁰^ORCID,Ríos-Tamayo Rafael¹¹^ORCID,Rosiñol Laura¹²^ORCID,Alvarez Rivas Miguel Angel¹³^ORCID,Bargay Joan¹⁴,Gonzalez-Rodriguez Ana Pilar¹⁵^ORCID,Alegre Adrián¹⁶^ORCID,Escalante Fernando¹⁷^ORCID,Iñigo Rodríguez María Belén¹⁸,De La Rubia Javier¹⁹²⁰²¹^ORCID,Teruel Ana Isabel²²^ORCID,de Arriba Felipe²³^ORCID,Palomera Luis²⁴^ORCID,Hernández Miguel T.²⁵^ORCID,Lopez Jiménez Javier²⁶^ORCID,Reinoso-Segura Marta²⁷^ORCID,García Mateo Aránzazu²⁸,Ocio Enrique M.²⁹^ORCID,Paiva Bruno³⁰^ORCID,Puig Noemi³¹^ORCID,Cedena M. Teresa³²^ORCID,Bladé Joan³³,Lahuerta Juan Jose³⁴^ORCID,San-Miguel Jesus F.³⁵^ORCID,

Affiliation:

1. Hematology Department, Hospital Universitario de Salamanca-IBSAL, CIBERONC and Centro de Investigación del Cáncer, IBMCC (USAL-CSIC), Salamanca, Spain

2. Hematology Department, Hospital 12 de Octubre, Medicine Department, Medicine School of Complutense University, I+12. CNIO, Madrid, Spain

3. Hematology Department, Cancer Center Clinica Universidad de Navarra (CCUN), Cima, CIBERONC, Pamplona, Spain

4. Hematology Department, Hospital Universitario de Salamanca-IBSAL, CIBERONC, Salamanca, Spain

5. Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain

6. Hematology Department, Hospital Clinico Universitario Santiago de Compostela, Santiago de Compostela, Spain

7. Clinical Hematology, Institut Català d’Oncologia and Josep Carreras Research Institute, Hospital Germans Trias I Pujol, Badalona, Spain

8. Hematology Department, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain

9. Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain

10. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain

11. Unidad de Gammapatías Monoclonales, Hospital Universitario Puerta de Hierro, Majadahonda, Spain

12. Hematology Department, Hospital Clinic, Barcelona, Spain

13. Servicio de Hematología y Hemoterapia, Hospital Universitario Reina Sofía, Córdoba, Spain

14. Hematology Department, Hospital Universitario Son Llatzer, IdISBa (Institut d’Investigació Sanitaria Illes Balears), Palma, Spain

15. Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain

16. Hematology Department, University Hospital La Princesa & University Hospital QuironSalud, Autonoma-University, Madrid, Spain

17. Servicio de Hematología, Unidad i+i, Complejo Asistencial Universitario de León, León, Spain

18. Hematology Department, Hospital Clínico San Carlos, Madrid, Spain

19. Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain

20. Universidad Católica de Valencia, Valencia, Spain

21. Centro de Investigación Biomédica en Red de Cáncer, CIBERONC CB16/12/00284, Instituto de Salud Carlos III, Madrid, Spain

22. Hematology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain

23. Servicio de Hematologia, Hospital Universitario Morales Meseguer, IMIB-Pascual Parrilla, Universidad de Murcia, Murcia, Spain

24. Hematology Department, Hospital Clínico Universitario Lozano Blesa, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain

25. Hematology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain

26. Hematology Department, Hospital Ramón y Cajal, Madrid, Spain

27. Hematology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Universidad de Sevilla, Sevilla, Spain

28. Hematology Department, Complejo Asistencial de Segovia, Segovia, Spain

29. Hematology Department, Hospital Universitario Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain

30. Hematology Department, Clinica Universidad de Navarra, Pamplona, Spain

31. Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain

32. Hematology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación i+12, Madrid, Spain

33. Hematology Department, Hospital Clinic, IDIBARS, Barcelona, Spain

34. Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain

35. Cancer Center Clinica Universidad de Navarra (CCUN), CIMA, IDISNA, CIBERONC, Pamplona, Spain

Abstract

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.

Publisher

American Society of Clinical Oncology (ASCO)

Link

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.23.02771

Reference20 articles.

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4. Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study

5. Lenalidomide plus Dexamethasone for High-Risk Smoldering Multiple Myeloma