Isatuximab-Specific Immunofixation Electrophoresis Assay to Remove Interference in Serum M-Protein Measurement in Patients with Multiple Myeloma.

Background: Isatuximab, an IgG-kappa (IgGκ) anti-cluster of differentiation 38 (CD38) monoclonal antibody approved for use in patients with relapsed or refractory multiple myeloma (MM), can potentially interfere with the visualization of endogenous monoclonal protein (M-protein) on standard immunofixation electrophoresis (IFE) and lead to inaccurate classification of a patient's response to therapy. The Hydrashift 2/4 isatuximab IFE assay (Hydrashift isatuximab assay) removes isatuximab interference from IFE. Using samples from patients enrolled in clinical trials of isatuximab-based therapy for MM, we demonstrate how the Hydrashift isatuximab assay improves the ability to detect residual M-protein and offer recommendations for when the assay is most useful.

Myeloma precursor disease (MGUS) among rescue and recovery workers exposed to the World Trade Center disaster.

An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA.

Immunotyping Provides Equivalent Results to Immunofixation in a Population with a High Prevalence of Monoclonal Gammopathies.

Background: Serum immunofixation (IF) is a common laboratory test used to diagnose and monitor patients with monoclonal gammopathies. Similarly, immunotyping (IT) by capillary electrophoresis can confirm the presence of a monoclonal protein (M-protein) and determine its isotype. The goal of this study was to compare the ability of IT and IF to detect M-proteins.

Use of a Daratumumab-Specific Immunofixation Assay to Assess Possible Immunotherapy Interference at a Major Cancer Center: Our Experience and Recommendations.

Background: The incorporation of monoclonal antibodies, such as daratumumab, into multiple myeloma treatment regimens has led to the issue of false-positive interference in both serum protein electrophoresis (SPEP) and immunofixation (IF). The Hydrashift assay removes daratumumab interference from IF, allowing for correct interpretation. Here, we retrospectively examined the use of the Hydrashift assay at a large cancer center and provide guidelines on its most appropriate use.

Dynamics of minimal residual disease in patients with multiple myeloma on continuous lenalidomide maintenance: a single-arm, single-centre, phase 2 trial.

Unlabelled: Background Lenalidomide maintenance improves progression-free survival for patients with multiple myeloma, although its optimal duration is unknown. Clearance of minimal residual disease (MRD) in the bone marrow results in superior outcomes, although its attainment or sustainment does not alter clinical decision-making. Studies that have evaluated MRD serially are limited in length.

Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial.

Importance: Recently, the benefit of adding daratumumab to the proteasome inhibitor-based, 3-drug combination of bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed multiple myeloma who underwent high-dose melphalan chemotherapy and autologous hemopoietic cell transplant was assessed. Here, we examine the addition of daratumumab to the second-generation proteasome inhibitor-based, 3-drug combination of carfilzomib, lenalidomide, and dexamethasone.

Objective: To assess the safety and effectiveness of carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy for patients with newly diagnosed multiple myeloma, in the absence of high-dose melphalan chemotherapy and autologous hemopoietic cell transplant.

Minimal residual disease in multiple myeloma: defining the role of next generation sequencing and flow cytometry in routine diagnostic use.

For patients diagnosed with multiple myeloma (MM) there have been significant treatment advances over the past decade, reflected in an increasing proportion of patients achieving durable remissions. Clinical trials repeatedly demonstrate that achieving a deep response to therapy, with a bone marrow assessment proving negative for minimal residual disease (MRD), confers a significant survival advantage. To accurately assess for minute quantities of residual cancer requires highly sensitive methods; either multiparameter flow cytometry or next generation sequencing are currently recommended for MM response assessment.

Using MALDI-TOF mass spectrometry in peripheral blood for the follow up of newly diagnosed multiple myeloma patients treated with daratumumab-based combination therapy.

Background: Daratumumab-based combination therapies have shown high rates of complete response (CR) and minimal residual disease negativity in patients with multiple myeloma. However, daratumumab, an IgGκ monoclonal antibody, interferes with electrophoretic techniques making it difficult to reliably define residual disease versus CR, especially in patients with IgGκ multiple myeloma.

Methods: Enrichment with polyclonal sheep antibody-coated magnetic microparticles combined with MALDI-TOF mass spectrometry (MALDI-TOF MS) analysis was used to detect M-proteins in serial samples from newly diagnosed multiple myeloma patients treated with daratumumab-based therapy.

Lifetime Pesticide Use and Monoclonal Gammopathy of Undetermined Significance in a Prospective Cohort of Male Farmers.

Background: Farmers have a higher incidence of multiple myeloma, and there is suggestive evidence of an elevated prevalence of its precursor, monoclonal gammopathy of undetermined significance (MGUS), relative to the general population. Pesticide exposures are suspected to play a role; however, the biologic plausibility for associations with multiple myeloma remains unclear.

Objectives: Our objectives were to examine the prevalence of MGUS and evaluate associations with a wide range of pesticides in a large sample of farmers.

Dickkopf-1 Can Lead to Immune Evasion in Metastatic Castration-Resistant Prostate Cancer.

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) with low androgen receptor (AR) and without neuroendocrine signaling, termed double-negative prostate cancer (DNPC), is increasingly prevalent in patients treated with AR signaling inhibitors and is in need of new biomarkers and therapeutic targets.

Methods: Candidate genes enriched in DNPC were determined using differential gene expression analysis of discovery and validation cohorts of mCRPC biopsies. Laboratory studies were carried out in human mCRPC organoid cultures, prostate cancer (PCa) cell lines, and mouse xenograft models.

Defining the undetectable: The current landscape of minimal residual disease assessment in multiple myeloma and goals for future clarity.

Multiple Myeloma, the second most prevalent hematologic malignancy, yet lacks an established curative therapy. However, overall response rate to modern four-drug regimens approaches 100%. Major efforts have thus focused on the measurement of minute quantities of residual disease (minimal residual disease or MRD) for prognostic metrics and therapeutic response evaluation.

Nested stromal epithelial tumor of the liver: A multidisciplinary approach to the treatment of an extremely rare malignancy.

Nested stromal epithelial tumor (NSET) of the liver is an extremely rare and unusual liver neoplasm with limited evidence of best practice for management. We report a 28-year-old male with NSET managed with primary partial hepatectomy with subsequent disease recurrence with follow-up metastectomy and successful radiofrequency ablation (RFA). Management of NSET of the liver requires a multidisciplinary approach.

Tracking of low disease burden in multiple myeloma: Using mass spectrometry assays in peripheral blood.

Efforts over the last 5 years have demonstrated that it is technically feasible to detect low levels of monoclonal proteins in peripheral blood using mass spectrometry. These methods are based on the fact that an M-protein has a specific amino acid sequence, and therefore, a specific mass. This mass can be tracked over time and can serve as a surrogate marker of the presence of clonal plasma cells.

Comparison of MALDI-TOF mass spectrometry analysis of peripheral blood and bone marrow-based flow cytometry for tracking measurable residual disease in patients with multiple myeloma.

Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) may soon replace routine electrophoretic methods for monitoring monoclonal proteins in patients with multiple myeloma. To further evaluate the clinical utility of this assay, we compared the performance of MALDI-TOF-MS head-to-head with an established bone marrow-based measurable residual disease assay by flow cytometry (Flow-BM-MRD), using Memorial Sloan Kettering Cancer Center's 10-color, single-tube method. Our results suggest that MALDI-TOF-MS adds value to bone marrow-based MRD testing and may be most useful for early detection of relapse in peripheral blood compared to current electrophoretic methods.

A novel method for the laboratory workup of anaphylactic transfusion reactions in haptoglobin-deficient patients.

Background: Patients with congenital haptoglobin deficiency can develop anti-haptoglobin antibodies after exposure to blood products, and they can suffer from life-threatening anaphylactic transfusion reactions. Here, we present a case of a 57-year-old Chinese male with myelodysplastic syndrome who manifested an anaphylactic transfusion reaction during the transfusion of platelets. The only abnormality detected during his reaction laboratory workup was an undetectable haptoglobin level in the absence of evidence of hemolysis.

Identification of gamma heavy chain disease using MALDI-TOF mass spectrometry.

We describe the use of MALDI-TOF mass spectrometry in the analysis of a suspected case of gamma heavy chain disease. The patient had an abnormal serum immunofixation result where a monoclonal gamma heavy chain band was present without a corresponding light chain. Analysis by MALDI-TOF mass spectrometry revealed large peaks in the spectrum following IgG-specific purification.

Distinguishing Drug from Disease by Use of the Hydrashift 2/4 Daratumumab Assay.

Background: Daratumumab, a monoclonal antibody used to treat relapsed or refractory multiple myeloma, can interfere with protein electrophoresis and immunofixation assays. False-positive immunofixation results due to daratumumab can cause uncertainty regarding the status of a patient's disease and lead to potential misclassification of their response to therapy. The Hydrashift 2/4 Daratumumab assay (Sebia) was recently cleared by the Food and Drug Administration for resolving daratumumab interference on immunofixation.

Evaluation of CisBio ELISA for Chromogranin A Measurement.

Background: Chromogranin A (CgA) is a nonspecific marker for the presence of neuroendocrine tumors and neuroendocrine differentiation. The objective of this study was to evaluate the performance of the CisBio CgA ELISA.

Methods: Precision, linearity, limit of blank, and recovery of the CisBio CgA ELISA were evaluated.

Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma.

Importance: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup.

Objective: To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS.

Pituitary as a Source of HCG: Residual Levels After Bilateral Testicular Tumor Removal.

Context: Challenging clinical scenario in which elevated β-human chorionic gonadotropin (HCG, subsequently termed HCG) levels suggested occult tumor metastases after removal of bilateral testicular cancers and metastases from them and as well as after chemotherapy.

Case Report: A 22-year-old male, post excision of bilateral testicular tumors, who had no imaging or clinical evidence of residual tumor but an elevated HCG raising the question of the presence and location of occult tumor metastases. Clinical Questions.

Standard Antithymocyte Globulin Dosing Results in Poorer Outcomes in Overexposed Patients after Ex Vivo CD34 Selected Allogeneic Hematopoietic Cell Transplantation.

Antithymocyte globulin (ATG) use mitigates the risk of graft rejection and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), but ATG overexposure in the setting of lymphopenia negatively affects immune recovery. We hypothesized that standard empiric weight-based dosing of ATG, used to prevent graft rejection in ex vivo CD34-selected allo-HCT, may lead to serious adverse consequences on outcomes in certain patients. We evaluated 304 patients undergoing myeloablative-conditioned ex vivo CD34-selected allo-HCT with HLA-matched donors for the treatment of hematologic malignancies.

MALDI-TOF mass spectrometry distinguishes daratumumab from M-proteins.

Background: Daratumumab, a therapeutic IgG kappa monoclonal antibody, can cause a false positive interference on electrophoretic assays that are routinely used to monitor patients with monoclonal gammopathies. In this study, we evaluate the ability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to distinguish daratumumab from disease-related IgG kappa monoclonal proteins (M-protein).

Methods: Waste clinical samples from 31 patients who were receiving daratumumab and had a history of IgG kappa monoclonal gammopathy were collected.

Mass spectrometry methods for detecting monoclonal immunoglobulins in multiple myeloma minimal residual disease.

Mass spectrometry methods that can detect low levels of monoclonal immunoglobulin in serum have recently been developed. These assays are based on the principle that each immunoglobulin has a unique amino acid sequence and therefore, has a unique mass. This mass can be used as a surrogate marker in order to monitor a patient's disease over time and at low levels.

Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster.

Importance: The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood.

Objective: To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS.