Observations from Mass-Fix: Prevalence and Characteristics of Therapeutic Monoclonal Antibodies (t-mabs) Detected by Isotyping of Monoclonal Immunoglobulins via MALDI-TOF Mass Spectrometry

Abstract

Abstract Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (“Mass-Fix”) has replaced serum immunofixation at our institution for detection of monoclonal immunoglobulins. One advantage of Mass-Fix is the ability to differentiate pathogenic endogenous monoclonal antibodies from therapeutic monoclonal antibodies (t-mabs), which are often the first-line treatment for multiple myeloma, by reviewing the light chain signature mass. The objective of this study was to describe the distribution of t-mabs and other key characteristics of clinical serum samples analyzed by Mass-Fix in 2022. Comprehensive results for each sample were extracted retrospectively from the laboratory information system. Of 66,710 total analyzed, 30,701 (46%) samples were reported as “positive” (i.e., contains a monoclonal protein), given the tertiary nature of our institution and reference laboratory services. The positive samples were further subdivided by t-mab (detected by Mass-Fix), with a total of 7,769 (25.3%) t-mabs reported. The top five IgG kappa t-mabs reported include daratumumab (n=6,537), elotuzumab or REGN5458/5459 (n=499), isatuximab (n=348), and rituximab (n=102). Rare observations included monoclonal proteins consistent with tixagevimab/ cilgavimab, for COVID-19 infection (n=7), obinutuzumab, an anti-CD20 t-mab for multiple sclerosis (n=1) and evolocumab, an IgG lambda anti-PCSK9 inhibitor (n=6). Of the 7,769 samples, the t-mab was the only reported clone in 47.7% of cases and was found along with the original disease-associated clone in remaining cases. When the original disease clone was present, it was an IgG kappa isotype 31% of the time and could have confounded the definition of complete therapy response for patients. 69% were non-IgG kappa original clones. Mass-Fix test orders have a multiple-choice prompt to provide any current therapy to aid in the patient’s result interpretation. For those samples where a t-mab was reported, the answer to this question regarding administered therapy was often discrepant from the report: only 38.5% of daratumumab-positive samples had an affirmation of daratumumab administration. The remaining 61.5% of daratumumab-positive samples reported an assortment of therapies, including bone marrow transplant, other t-mabs, no active therapy, or the field was left blank, highlighting poor compliance. Additionally, 154/36,009 samples where the provider affirmed daratumumab administration were reported as negative (i.e., no monoclonal protein observed on Mass-Fix). Often, the send-out laboratory does not have medical record access where treatment information is detailed. In conclusion, we reported the presence of a t-mab in 11.6% of all samples tested with Mass-Fix, suggesting that t-mabs have entered the clinical practice to stay, and accurately determining their presence in the challenging environment of poor compliance to prompt questions and evolving treatment regimens is something that cannot be ignored by clinical laboratories. Mass-Fix allows detection of a t-mab in the same routine run as other testing, without need of a second immunofixation to rule out the IgG kappa finding is not a t-mab.