Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation

Author:

Paiva Bruno1,Vidriales Maria-Belén12,Cerveró Jorge1,Mateo Gema12,Pérez Jose J.1,Montalbán Maria A.3,Sureda Anna4,Montejano Laura3,Gutiérrez Norma C.12,de Coca Alfonso García5,de las Heras Natalia6,Mateos Maria V.12,López-Berges Maria C.1,García-Boyero Raimundo7,Galende Josefina8,Hernández Jose9,Palomera Luis10,Carrera Dolores11,Martínez Rafael12,de la Rubia Javier13,Martín Alejandro14,Bladé Joan15,Lahuerta Juan J.3,Orfao Alberto216,San Miguel Jesús F.12

Affiliation:

1. Hospital Universitario de Salamanca, Salamanca;

2. Centro de Investigación del Cáncer (CIC, IBMCC USAL-CSIC), Salamanca;

3. Hospital 12 de Octubre, Madrid;

4. Hospital Santa Creu I Sant Pau, Barcelona;

5. Hospital Clínico Universitario de Valladolid, Valladolid;

6. Complejo Hospitalario de León, León;

7. Hospital General de Castellón, Castellón;

8. Hospital del Bierzo, Ponferrada;

9. Hospital General de Segovia, Segovia;

10. Hospital Lozano Blesa, Zaragoza;

11. Hospital Central de Asturias, Oviedo;

12. Clínico San Carlos, Madrid;

13. Hospital La Fe, Valencia;

14. Hospital Virgen de la Concha, Zamora;

15. Hospital Clínic, Institut d'Investigaciones Biomediques August Pi i Sunyer, Barcelona; and

16. Servicio General de Citometría, Universidad de Salamanca, Salamanca, Spain

Abstract

Abstract Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol VBMCP/VBAD induction plus autologous stem cell transplantation [ASCT]). MRD status by MFC was determined at day 100 after ASCT. Progression-free survival (PFS; median 71 vs 37 months, P < .001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD negative versus MRD positive at day 100 after ASCT. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation-negative complete response after ASCT. Moreover, MRD− immunofixation-negative (IFx−) patients and MRD− IFx+ patients had significantly longer PFS than MRD+ IFx− patients. Multivariate analysis identified MRD status by MFC at day 100 after ASCT as the most important independent prognostic factor for PFS (HR = 3.64, P = .002) and OS (HR = 2.02, P = .02). Our findings demonstrate the clinical importance of MRD evaluation by MFC, and illustrate the need for further refinement of MM re-sponse criteria. This trial is registered at http://clinicaltrials.gov under identifier NCT00560053.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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