PB2100 MULTI‐BIOMARKER NORMALIZATION OF MM SERUM PATIENTS AS POSSIBLE GATEWAY FOR BONE MARROW MRD BY MULTIPARAMETER FLOW CYTOMETRY
Authors: C. Quiñones‐Torrelo, A. I. Teruel Casasus, N. Carvalho
Journal: HemaSphere (2019)

Background: With the continuous development of more effective treatments and with new mechanisms of action leading to deeper responses of patients with Multiple Myeloma, the use of more sensitive tools to evaluate the effectiveness of treatments is required. Minimal residual disease by bone marrow multiparametric flow cytometry (BMMFC) has progressively gained wide acceptance and is presently the final goal of treatment. However, the acquisition of bone marrow remains a limitation due to its invasive nature. The incorporation to the laboratory routine of automated more sensitive techniques for the quantification of the monoclonal protein (MP), as serum free light chains (sFLC) and Heavy‐light chains assays (HLC) have increased the sensitivity to detect blood circulating monoclonal proteins. Aims: To investigate if a correlation exists between BMMFC minimal residual disease (MRD) and a panel of serological MP biomarkers. The hypothesis is that a non‐negative panel of biomarkers is a good surrogate for positive BM MRD by MFC. Methods Paired BM and serum samples were analyzed, respectively by 8 ‐ color MFC and by the serum monoclonal protein biomarker panel. The serum MP biomarker panel was composed by immunofixation (sIFE), serum free light chains (sFLC) and the Hevylite assay that targets heavy + light chain immunoglobulin isotypes. Regarding sIFE, two different approaches have been carried out when interpreting results of the presence of possible oligoclonal bands (OCB): 1 ‐ sIFE with possible OCB were considered positive and by consequence an abnormal marker on the serum panel; 2 ‐ the oligoclonality seen on the sIFE had to be confirmed by the normalization of both the sFLC and HLC assays, i.e., patients with OCB but normal FLC and HLC ratios were considered as normal. Positive (PPV) and negative predictive values (NPV) were calculated by Fisher exact test. Results: 43 paired samples were analyzed. Twenty‐one out of 41 (51%) BM samples were MRD negative. Of the 12 possible OCB observed in sIFE, 4 were MRD positive and 4 were negative by FLC and HLC. Of these, only one was positive by BM MRD. Contingency tables were created to compare the serum biomarker panel results vs BM MRD. When the OCB were considered as an abnormal sIFE result, we found a PPV of 0.95 and NPV of 0.24, however, no statistical significance was found (p = 0.1836). When OCB were interpreted on the basis of the sFLC and HLC results, a significant statistically result was achieved (p = 0.0002) with a PPV of 0.95 (CI: 0.7513‐0.9987) and an NPV of 0.62 (CI: 0.3844–0.8189). The specificity found to predict BM positive MRD was 0.93 (CI: 0.6613 ‐0.9982). Summary/Conclusion: Our results suggest that the proposed serum MP biomarker panel composed by sIFE + sFLC + HLC might be sensitive enough to guide clinicians to more selective requests of BM MRD. Also, in cases where probable OCB bands are found on the sIFE, the normalization of the sFLC and HLC ratio can help in the interpretation of a real phenomenon of oligoclonality. Further studies are required to validate these results mainly with a greater number of samples and follow‐up time.