Measuring MRD in Myeloma Patients with Bloodflow Method

Dr. Laura Notarfranchi presents the results of ultra-sensitive assessment of Measurable Residual Disease (MRD) in Peripheral Blood (PB) of multiple myeloma patients using Bloodflow

Abstract title:

Ultra-Sensitive Assessment of Measurable Residual Disease (MRD) in Peripheral Blood (PB) of Multiple Myeloma (MM) Patients Using Bloodflow

Purpose of the trial:

Assessing MRD in bone marrow (BM) using next-generation flow (NGF) or sequencing precludes periodic evaluations because of its invasiveness. MRD assessment in PB could overcome this limitation, but its clinical value is not established and the negative predictive value (NPV) when compared to BM is <70%. This is because tumor burden in PB is ~3log lower than in BM, and methods capable of detecting MRD below 10-6 are thus needed for improved concordance.

Video summary:

MRD was evaluated using NGF in PB of 138 MM patients (pts) enrolled in the GEM2014MAIN trial. PB samples were collected after the second year of maintenance, when pts stopped treatment if MRD negative (in BM), or continued on therapy for three additional years if MRD positive at that time. Reaching a minimum sensitivity of 10-7 requires analyzing ≥ 2x108 cells (~50mL of PB). To avoid high staining costs and impractically long acquisition periods, a new method integrating immunomagnetic enrichment using MACS® MicroBeads prior NGF was developed and coined as BloodFlow. Large (~50mL) PB volumes were magnetically labeled and processed via MACS® columns, and ~100µL aliquots enriched with circulating plasma cells (PC) were analyzed using EuroFlow NGF. The concordance between MRD assessment using BloodFlow (in PB) vs NGF (in PB and/or BM) was analyzed in 389 samples from 351 MM pts.

Conclusions:

MRD assessment in PB using NGF was prognostic in pts under maintenance or observation. Notwithstanding, a new method (BloodFlow) was developed to increase the NPV and showed an unprecedented sensitivity to detect MRD down to 10-8 in PB. BloodFlow detected MRD in PB more frequently than NGF, with a consequent decrease in the number of cases with persistent MRD in BM while undetectable in PB, which were more frequent during early and intensive treatment stages. These results suggest the possibility of periodic and ultra-sensitive MRD assessment in PB during maintenance/observation.

Trial information:

ASH 2022: Abstract #865

Authors:

Laura Notarfranchi, MD, Anastasia Zherniakova, Marta Lasa, PhD, Noemi Puig, MD, PhD, María Teresa Cedena, MD, PhD, Joaquin Martinez-Lopez, MD PhD, María José Calasanz, PhD, Diego Alignani, PhD, Leire Burgos, Irene Manrique, Yi-Ju Huang, Jochen Fracowiak, Clara Gomez, Felipe De Arriba, PhD, Paula Rodríguez-Otero, MD, PhD, Luis Palomera, MD, PhD, Anna Sureda, Maria Esther Clavero Sanchez, Miguel Angel Alvarez, Angela Ibanez Garcia, Miguel-Teodoro Hernández, MD, PhD, Albert Perez, Ana Pilar Gonzalez, PhD, Enrique M. Ocio, Juan Flores-Montero, Alberto Orfao, MD, PhD, Juan Jose Lahuerta, MD, PhD, María-Victoria Mateos, MD, PhD, Laura Rosiñol, MD, PhD, Joan Bladé Creixenti, MD, PhD, Jesús San-Miguel, MD, PhD and Bruno Paiva