Minimal residual disease monitoring and immune profiling using second generation flow cytometry in elderly multiple myeloma
Paiva B (1), Cedena MT (2), Puig N (3), Arana P (1), Vidriales MB (3), Cordon L (4), Flores-Montero J (5), Gutierrez NC (3), Martín-Ramos ML (2), Martinez-Lopez J (2), Ocio EM (3), Hernandez MT (6), Teruel AI (7), Rosiñol L (8), Echeveste MA (9), Martinez R (10), Gironella M (11), Oriol A (12), Cabrera C (13), Martin J (14), Bargay J (15), Encinas C (16), Gonzalez Y (17), Van Dongen JJ (18), Orfao A (5), Bladé J (8), Mateos MV (3), Lahuerta JJ (2), San Miguel JF (19).
(1) Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain;
(2) Hospital Universitario 12 de Octubre, Instituto de investigacion 12 de Octubre, Madrid, Spain;
(3 )Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigacion del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain;
(4) Hospital Universitario y Politecnico La Fe, Valencia, Spain;
(5) Servicio General de Citometria-NUCLEOS, Centro de Investigacion del Cancer (IBMCC-USAL, CSIC), IBSAL and Department of Medicine, Universidad de Salamanca, Salamanca, Spain;
(6) Hospital Universitario de Canarias, Tenerife, Spain;
(7) Hospital Clinico de Valencia, Valencia, Spain;
(8) Hospital Clinic, IDIBAPS, Barcelona, Spain;
(9) Hospital de Donostia, San Sebastian, Spain;
(10) Hospital Clinico San Carlos, Madrid, Spain;
(11) Hospital Vall d'Hebron, Barcelona, Spain;
(12 )Institut Catala d'Oncologia, Institut Josep Carreras, Hospital Germans Trias I Pujol, Badalona, Spain;
(13) Hospital San Pedro de Alcantara, Caceres, Spain;
(14) Hospital General Virgen del Rocio, Sevilla, Spain;
(15)Hospital Sont Llatzer, Palma de Mallorca, Spain;
(16) Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon (IiSGM), Madrid, Spain;
(17) Institut d'Oncologia Dr. Josep Trueta, Girona, Spain;
(18) Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, Netherlands.
19Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain
The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible than elderly patients. Since an optimal balance between treatment efficacy and toxicity is of utmost importance in elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population.
Here, we used 2nd generation 8-color multiparameter-flow-cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study.
The transition from 1st to 2nd generation MFC resulted in increased sensitivity, and allowed to identify three patient groups according to MRD levels: MRD-negative (<10-5; n=54, 34%), MRD-positive between <10-4 and ≥10-5 (n=20, 12%), and MRD-positive ≥10-4 (n=88, 54%).
MRD status was an independent prognostic factor for time-to progression (-TTP- HR:2.7; P=.007) and overall survival (-OS- HR:3.1; P=.04) with significant benefit for MRD-negative patients (median TTP not reached, 70% OS at 3-years), and similar poorer outcomes for cases with MRD levels between <10-4 and ≥10-5 vs ≥10-4 (both median TTP of 15 months; 63% and 55% OS at 3-years). Furthermore, MRD-negativity significantly improved TTP of patients >75-years (HR:4.8; P<.001), and those with high-risk cytogenetics (HR:12.6; P=.01).
Using 2nd generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate and favorable outcome (25%, 61% and 100% OS at 3-years; P=.01); the later patients being characterized by an increased compartment of mature B-cells.
Our results show that similarly to transplant-candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM, irrespectively of patients' age and cytogenetic risk.
CITATION Blood. 2016 Apr 26. pii: blood-2016-03-705319