P-037: Serum-free light chain and heavy-light chains normalization as markers for negative measurable residual disease in Multiple Myeloma after autologous stem cell transplant

Abstract

<h3>Background</h3> Measurable residual disease (MRD) in Multiple Myeloma is widely recognized of significant importance in prognosis. Multi-parameter flow cytometry (MFC) on bone marrow is one of the most chosen techniques to evaluate MRD. Nonetheless, it needs a bone marrow aspiration and time points could be limited due to the invasiveness of the evaluation. Serum-free light chains (sFLC) and heavy-light chains (HLC) assays have high sensitivity to detect blood circulating monoclonal proteins and infer immune reconstitution. They could be used as a peripheral surrogate marker for MRD. <h3>Aim</h3> Evaluate the correlation between the MFC-MRD negativity and the normalization of sFLC and sHLC in patients with MM after autologous stem cell transplant (ASCT). <h3>Methods</h3> 27 patients transplanted with IgG or IgA MM were included in this analysis. y. Assays (sFLC, sFLC on serum; MFC on bone marrow) were performed on all patients at a median of 100 days post-ASCT. The kappa/lambda sFLC ratio (FLCr) and involved/uninvolved HLC ratio (HLCr) were used to assess responses using published normal ranges. International Myeloma Working Group (IMWG) response criteria were used to classify treatment responses. MFC was performed according to the Euroflow panel with 10^-5 sensitivity. Contingency tables were used to compare the serum biomarkers versus the MRD. Positive (PPV) and negative predictive value (NPV) were calculated by Fisher exact. <h3>Results</h3> HLCr normalized in 18/27 (67%) patients, with FLCr normalization in 13/27 (48%) at 100 days post-ASCT. MFC-MRD negativity at 100 days post-ASCT was noted in 15/27 (56%). Patients. Post-ASCT HLCr and FLCr normalization was found in 9 patients (60%) with MRD negativity. Comparization of MFC MRD negativity and HLCr and FLCr normalization tests showed 86.7% sensitivity, 58.3% specificity, 72% PPV, and 77% NPV (Fisher Test p=0.037). <h3>Conclusions</h3> Despite the high percentage of patients with normal HLCr and FLCr in patients in MRD negativity at day 100 post-ASCT, ours results demonstrates that HLCr and FLCr normalization does lack sensitivity when compared to MFC-MRD. HCLr and FLCr could be used in patients with negative MRD to follow patients in more time points to predict relapse and prompt a bone marrow MRD evaluation. This work will be validated in a larger cohort of post-ASCT multiple myeloma patients, taking into account follow-up, namely prediction of relapse and progression-free survival.