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Peripheral blood-based disease monitoring by mass spectrometry in patients with multiple myeloma

Dr. Puig Morón

Noemí Puig Morón


Institute of Biomedical Research from Salamanca

Project Term: July 1, 2022 - June 30, 2025

The present project will investigate the ability of quantitative immune precipitation mass spectrometry (QIP-MS) to anticipate relapsed or progressive disease in peripheral blood samples from patients with multiple myeloma. In the context of the GEM2014MAIN trial (lenalidomide and dexamethasone plus or minus ixazomib as maintenance), we will assess the presence of disease by QIP-MS in parallel with conventional methods in serum and next generation flow in bone marrow samples.

Lay Abstract

This project will be performed with samples obtained from patients included in the GEM2014MAIN trial for newly diagnosed patients with multiple myeloma (MM) previously included in the GEM2012MENOS65 and having responded favorably to the treatment, which includes an autologous stem cell transplantation. 371 patients have been enrolled and randomly assigned to receive lenalidomide and dexamethasone plus or minus ixazomib during at least two years that could have been extended three more if the patient was found to have residual disease in the bone marrow (BM) evaluation planned after the first two.

One of the aims of the GEM2014MAIN is to analyze the evolution and clinical value of the assessment of minimal residual disease (MRD) in the BM and in fact, the protocol includes a yearly evaluation by highly sensitive flow cytometry for five years after enrollment. During the first two years, patients are evaluated monthly using conventional methods such as serum protein electrophoresis and immunofixation (SPEP/IFE), free light chains and PET imaging when appropriate and afterwards, patients found to have residual disease in the BM will continue to be evaluated monthly and if found to be negative every three months. This scenario is very well suited to investigate whether or not quantitative immune precipitation mass spectrometry (QIP-MS) is able to identify the presence of disease in peripheral blood earlier and better than conventional and BM based methods, in our case by highly sensitive flow cytometry (or Next Generation Flow, NGF). QIP-MS is a highly sensitive and specific method able to identify the monoclonal protein produced and secreted by the malignant plasma cells based on its unique molecular mass. Our group and others have recently shown its higher sensitivity as compared to standard SPEP/IFE, and comparable results to those produced by NGF and next generation sequencing in BM samples obtained at different time-points throughout treatment. However, to our knowledge, there are no large studies analyzing the value of QIP-MS as peripheral-blood based method for patients monitoring. For this purpose, we will analyze the presence of disease in parallel by SPEP/IFE and QIP-MS in serum samples and by NGF in the BM samples obtained yearly as per protocol. We aim to anticipate relapsed or progressive disease using QIP-MS as compared to conventional and/or highly sensitive techniques applied in BM, such as NGF in our case.

Early detection of relapsed or progressive disease allows an early treatment, which has already demonstrated to improve patients´ outcome and is currently being tested in various clinical trials. The use of QIP-MS in this regard would also elude the need of repeating BM aspirations, thus permitting a frequent monitoring that potentially avoids false negative results due to hemodilution and the patchy nature of MM infiltration.

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