Identification of Friend or Foe: The Laboratory Challenge of Differentiating M-Proteins from Monoclonal Antibody Therapies

Abstract

Background: Since the first monoclonal antibody (mAb) therapy hit the market in 1996, the number of disorders treated with this class of therapeutics has seen tremendous growth, with over 50 antibodybased therapeutics currently approved for use in the US and Europe. This class of therapeutics recently made profound progress in the treatment of refractory multiple myeloma (MM). Treating MM with the mAbs will challenge the laboratory's ability to differentiate exogenous mAbs being used to treat patients from endogenous mAbs associated with disease. Content: An overview of the therapeutic mAbs (t-mAbs) developed for the treatment of MM is provided. The anticipated impact of these therapies on patient care, laboratory testing, and clinical research is discussed. Efforts underway to develop strategies and technologies to help laboratories address the growing challenge of mAb interferences are reviewed. Summary: Laboratories can implement risk mitigation strategies at the preanalytical and postanalytical phase of testing to reduce the likelihood of reporting false-positive M-protein results in patients receiving t-mAbs. However, at the analytical phase of testing, current laboratory methods are ill-suited to differentiate between residual disease and residual drugs. Mass spectrometrybased methods might be best positioned to aid laboratories with the rapidly evolving landscape of MM treatment. IMPACT STATEMENT Patients being screened for monoclonal gammopathies, and those diagnosed with MM and currently undergoing treatment with t-mAbs will benefit from raised awareness of the potential for false-positive M-protein results due to t-mAbs. Here, an informational resource is provided to foster a better understanding of when t-mAbs are likely to be encountered and how the associated risk can be mitigated. This article reviews the emerging role of mass spectrometry as a method of measuring M-proteins and why this is less likely to be negatively affected by t-mAbs compared to current testing methods.

An unusual pattern in serum protein electrophoresis to take in mind: A case report

“…However, this is an innovative approach that could be considered as reference method in the future. On the other hand, protein electrophoresis and IFE are increasingly more common and some helpful measures to avoid t-mAbs interferences in traditional methods for monoclonal protein detection can be used [ 24 ].…”

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

“…However, in ELOQUENT-2, 10 mg/ kg was continued every 2 weeks for cycles 3 and beyond whereas in ELOQUENT-3, elotuzumab was given 20 mg/ kg intravenous every 4 weeks for cycle 3 and beyond. Similar to other therapeutic antibodies, elotuzumab may interfere with protein electrophoresis or immunofixation measurements, 89 causing false positives for M-spike results in the peripheral blood and potentially affecting the assessment of response according to the International Myeloma Working Group (IMWG) criteria. Unlike with dara, gel-shift approaches have not yet been developed to eliminate false positives for elotuzumab.…”

Therapeutic Monoclonal Antibodies in the Clinical Laboratory

“…Immunotherapies are a hot topic, with the potential to affect our understanding of the immune system and treat a diverse array of conditions previously thought untreatable. Therapeutic monoclonal antibodies (mAbs) 2 are part of this revolution, and around 60 of them are approved by the Food and Drug Administration. Clinical chemists are poised for change and are aware of the success of the biologic drugs.…”

“…The finding of a monoclonal protein, even if small, usually triggers additional costly and invasive investigations, such as biopsies of bone marrow, kidney, or heart. With the approval of 2 mAbs for treatment of myeloma (daratumumab and elotuzumab) and others in the pipeline, the visualization of an iatrogenic IgG κ monoclonal protein corresponding to the mAb has become a common finding in high-volume immunology laboratories (2,3). In the absence of clinical history or medication records, an incidental finding of IgG κ may suggest a monoclonal gammopathy of undetermined significance, the most prevalent premalignant monoclonal gammopathy.…”