B-183 Teclistamab: a bispecific monoclonal IgG lambda therapeutic is observable on serum immunofixation and mass-fix Article Swipe

Background Monoclonal antibody therapies (t-mabs) are known to interfere in serum immunofixation, as they show up as a discrete band. Until recently, most of the t-mabs were IgG kappa monoclonal immunoglobulins, and laboratories were familiar with the clue of a cathodal migrating IgG kappa in a patient sample, suggesting this could be daratumumab or another t-mab in the report. However, with the advent of novel antibody-based medications, identification via traditional laboratory methods has grown more complex. Teclistamab-cqyv is an IgG4 lambda T-cell engager bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3 on T cells, used in relapsed and refractory multiple myeloma. The goal of this study was to determine if teclistamab could be detected on serum immunofixation and mass-fix. Methods Residual waste serum samples with no monoclonal protein via mass-fix (a MALDI-TOF based assay used in place of serum immunofixation) and variable polyclonal background were used to spike teclistamab (n=3). Briefly, one sample had total IgG < 500 mg/dL measured by nephelometry on a Siemens BNII (431 mg/dL, hypo gamma), a second sample had IgG within reference intervals (779 mg/dL, normal gamma) and the third sample had IgG > 1600 mg/dL (1950 mg/dL, polyclonal hypergamma). Each sample was divided into 3 aliquots and spiked with teclistamab (Tecvayli, Johnson &Johnson) obtained from the pharmacy, at final concentrations of 10, 20, and 40 mg/dL in the serum samples. The nine artificial samples were subjected to immunofixation electrophoresis (Sebia) and a new monoclonal protein study using mass-fix, a laboratory developed test. Results In the serum immunofixation experiments, a single discrete IgG lambda band was visible in the hypogamma and normal gamma samples (Table 1) when teclistamab was present at 20 mg/dL or 40 mg/dL. No bands were observed for the 10 mg/dL spike in hypos or normals. No teclistamab was detected at any concentration in the hypergamma sample. When mass-fix was performed, monoclonal protein spikes consistent with the expected mass of the two unique lambda light chains associated with teclistamab (22624Da and 22636Da) were identified in the hypo and normal gamma samples at the 3 concentrations tested: 10, 20, and 40 mg/dL. No mass-fix spikes were seen above the polyclonal spectra in the hypergamma samples. Conclusion The polyclonal background of immunoglobulins in a serum specimen plays a significant role in the identification of any monoclonal protein. Teclistamab is a new IgG lambda t-mab with potential to show up as an interference in both immunofixation and mass-fix, depending on the amount of polyclonal IgG present. Without positive identification, teclistamab presence could complicate interpretation of a patient’s response to treatment. This proof-of-concept study shows that mass-fix can detect smaller concentrations of teclistamab than immunofixation, therefore would be more prone to identifying this t-mab than labs employing the gel-based immunofixation method.