{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T02:49:04Z","timestamp":1786416544979,"version":"build-2736575974"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Isatuximab, an IgG-kappa (IgG\u03ba) 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\u2019s 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Samples from 141 patients with a variety of known M-protein isotypes were selected and analyzed by standard IFE and the Hydrashift isatuximab assay. A positive control containing isatuximab was run on every standard IFE and Hydrashift gel.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The Hydrashift isatuximab assay reliably shifted the migration of isatuximab in patient samples. Standard IFE was adequate for determining 104 patients\u2019 M-protein status, and the Hydrashift isatuximab assay confirmed these results. In samples from 37 patients with a history of IgG\u03ba MM and a single IgG\u03ba band visible on standard IFE near the isatuximab migration site, the Hydrashift isatuximab assay was able to separate isatuximab from endogenous M-protein, identifying residual M-protein in 17 samples and preventing false-positive interpretations of standard IFE in 20 samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The Hydrashift isatuximab assay is most useful in patients with known IgG\u03ba MM when a single IgG\u03ba band appears near the isatuximab migration site on standard IFE during isatuximab-based therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>ClinicalTrials.gov Registration Numbers<\/jats:title>\n                  <jats:p>NCT03275285 and NCT03319667.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jalm\/jfae028","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T17:34:44Z","timestamp":1712252084000},"page":"661-671","source":"Crossref","is-referenced-by-count":10,"title":["Isatuximab-Specific Immunofixation Electrophoresis Assay to Remove Interference in Serum M-Protein Measurement in Patients with Multiple Myeloma"],"prefix":"10.1093","volume":"9","author":[{"given":"Katie","family":"Thoren","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center , New York, NY , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Menad","sequence":"additional","affiliation":[{"name":"Sebia , Lisses , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Nouadje","sequence":"additional","affiliation":[{"name":"Sebia , Lisses , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Mac\u00e9","sequence":"additional","affiliation":[{"name":"Sanofi R&D , Chilly-Mazarin , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"2024070115213836300_jfae028-B1","author":"American Cancer Society Cancer Statistics Center"},{"key":"2024070115213836300_jfae028-B2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann Oncol"},{"key":"2024070115213836300_jfae028-B3","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3324\/haematol.2015.127860","article-title":"Health-related quality of life in patients with multiple myeloma\u2013does it matter?","volume":"100","author":"Kvam","year":"2015","journal-title":"Haematologica"},{"key":"2024070115213836300_jfae028-B4","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1038\/leu.2013.185","article-title":"Review of health-related quality of life data in multiple myeloma patients treated with novel agents","volume":"27","author":"Sonneveld","year":"2013","journal-title":"Leukemia"},{"key":"2024070115213836300_jfae028-B5","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.3324\/haematol.2014.117176","article-title":"European Myeloma Network guidelines for the management of multiple myeloma-related complications","volume":"100","author":"Terpos","year":"2015","journal-title":"Haematologica"},{"key":"2024070115213836300_jfae028-B6","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.3390\/cancers12123576","article-title":"Recent advances in the treatment of patients with multiple myeloma","volume":"12","author":"Legarda","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2024070115213836300_jfae028-B7","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.3390\/cancers12113488","article-title":"Shaping the treatment paradigm based on the current understanding of the pathobiology of multiple myeloma: an overview","volume":"12","author":"Ninkovic","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2024070115213836300_jfae028-B8","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.clml.2018.06.015","article-title":"The multiple myeloma drug pipeline-2018: a review of small molecules and their therapeutic targets","volume":"18","author":"Abramson","year":"2018","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"2024070115213836300_jfae028-B9","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41408-020-00359-2","article-title":"Multiple myeloma current treatment algorithms","volume":"10","author":"Rajkumar","year":"2020","journal-title":"Blood Cancer J"},{"key":"2024070115213836300_jfae028-B10","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1007\/s00277-022-04917-5","article-title":"Anti-CD38 antibody therapy for patients with relapsed\/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes","volume":"101","author":"Leleu","year":"2022","journal-title":"Ann Hematol"},{"key":"2024070115213836300_jfae028-B11","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1177\/10781552221107850","article-title":"Pharmacy considerations: use of anti-CD38 monoclonal antibodies in relapsed and\/or refractory multiple myeloma","volume":"29","author":"Shah","year":"2023","journal-title":"J Oncol Pharm Pract"},{"key":"2024070115213836300_jfae028-B12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s40265-015-0536-1","article-title":"Daratumumab: first global approval","volume":"76","author":"McKeage","year":"2016","journal-title":"Drugs"},{"key":"2024070115213836300_jfae028-B13","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s40265-020-01311-1","article-title":"Isatuximab: first approval","volume":"80","author":"Dhillon","year":"2020","journal-title":"Drugs"},{"key":"2024070115213836300_jfae028-B14","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.1158\/1078-0432.CCR-14-0695","article-title":"SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies","volume":"20","author":"Deckert","year":"2014","journal-title":"Clin Cancer Res"},{"key":"2024070115213836300_jfae028-B15","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1158\/1078-0432.CCR-18-1597","article-title":"The mechanism of action of the anti-CD38 monoclonal antibody isatuximab in multiple myeloma","volume":"25","author":"Moreno","year":"2019","journal-title":"Clin Cancer Res"},{"key":"2024070115213836300_jfae028-B16","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.3389\/fimmu.2020.01771","article-title":"Isatuximab acts through Fc-dependent, independent, and direct pathways to kill multiple myeloma cells","volume":"11","author":"Zhu","year":"2020","journal-title":"Front Immunol"},{"key":"2024070115213836300_jfae028-B17","author":"Sanofi-Aventis U.S. LLC"},{"key":"2024070115213836300_jfae028-B18","doi-asserted-by":"crossref","first-page":"112166","DOI":"10.18632\/oncotarget.22992","article-title":"Targeting CD38 alleviates tumor-induced immunosuppression","volume":"8","author":"Tai","year":"2017","journal-title":"Oncotarget"},{"key":"2024070115213836300_jfae028-B19","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(19)32556-5","article-title":"Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study","volume":"394","author":"Attal","year":"2019","journal-title":"Lancet"},{"key":"2024070115213836300_jfae028-B20","author":"European Medicines Agency (EMA)"},{"key":"2024070115213836300_jfae028-B21","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/S0140-6736(21)00592-4","article-title":"Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial","volume":"397","author":"Moreau","year":"2021","journal-title":"Lancet"},{"key":"2024070115213836300_jfae028-B22","author":"Japan Pharmaceuticals and Medical Devices Agency"},{"key":"2024070115213836300_jfae028-B23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1182\/blood-2020-136613","article-title":"Development of a Hydrashift 2\/4 isatuximab assay to mitigate interference with monoclonal protein detection on immunofixation electrophoresis in vitro diagnostic tests in multiple myeloma","volume":"136","author":"Finn","year":"2020","journal-title":"Blood"},{"key":"2024070115213836300_jfae028-B24","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.clinbiochem.2016.09.015","article-title":"Treatment of multiple myeloma with monoclonal antibodies and the dilemma of false positive M-spikes in peripheral blood","volume":"51","author":"Murata","year":"2018","journal-title":"Clin Biochem"},{"key":"2024070115213836300_jfae028-B25","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1177\/00045632211062080","article-title":"Case report: interference from isatuximab on serum protein electrophoresis prevented demonstration of complete remission in a myeloma patient","volume":"59","author":"Wheeler","year":"2022","journal-title":"Ann Clin Biochem"},{"key":"2024070115213836300_jfae028-B26","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.3324\/haematol.2018.189159","article-title":"European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when","volume":"103","author":"Caers","year":"2018","journal-title":"Haematologica"},{"key":"2024070115213836300_jfae028-B27","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1016\/S1470-2045(16)30206-6","article-title":"International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma","volume":"17","author":"Kumar","year":"2016","journal-title":"Lancet Oncol"},{"key":"2024070115213836300_jfae028-B28","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/jalm\/jfab055","article-title":"Use of a daratumumab-specific immunofixation assay to assess possible immunotherapy interference at a major cancer center: our experience and recommendations","volume":"6","author":"Kirchhoff","year":"2021","journal-title":"J Appl Lab Med"},{"key":"2024070115213836300_jfae028-B29","author":"FDA"},{"key":"2024070115213836300_jfae028-B30","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1515\/cclm-2015-1023","article-title":"Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation","volume":"54","author":"Willrich","year":"2016","journal-title":"Clin Chem Lab Med"},{"key":"2024070115213836300_jfae028-B31","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1373\/clinchem.2010.152116","article-title":"Interference of monoclonal antibody therapies with serum protein electrophoresis tests","volume":"56","author":"McCudden","year":"2010","journal-title":"Clin Chem"},{"key":"2024070115213836300_jfae028-B32","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1373\/jalm.2018.026476","article-title":"Distinguishing drug from disease by use of the Hydrashift 2\/4 daratumumab assay","volume":"3","author":"Thoren","year":"2019","journal-title":"J Appl Lab Med"},{"key":"2024070115213836300_jfae028-B33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.clinbiochem.2021.02.011","article-title":"Clearing drug interferences in myeloma treatment using mass spectrometry","volume":"92","author":"Kohlhagen","year":"2021","journal-title":"Clin Biochem"},{"key":"2024070115213836300_jfae028-B34","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1182\/blood-2018-05-848986","article-title":"A universal solution for eliminating false positives in myeloma due to therapeutic monoclonal antibody interference","volume":"132","author":"Mills","year":"2018","journal-title":"Blood"},{"key":"2024070115213836300_jfae028-B35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.cca.2019.02.017","article-title":"MALDI-TOF mass spectrometry distinguishes daratumumab from M-proteins","volume":"492","author":"Moore","year":"2019","journal-title":"Clin Chim Acta"},{"key":"2024070115213836300_jfae028-B36","doi-asserted-by":"crossref","first-page":"15236","DOI":"10.1021\/acs.analchem.1c03410","article-title":"Validated method based on immunocapture and liquid chromatography coupled to high-resolution mass spectrometry to eliminate isatuximab interference with M-protein measurement in serum","volume":"93","author":"Muccio","year":"2021","journal-title":"Anal Chem"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/9\/4\/661\/58379378\/jfae028.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/9\/4\/661\/58379378\/jfae028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T18:22:33Z","timestamp":1719858153000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/9\/4\/661\/7640895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,4]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,4]]},"published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jalm\/jfae028","relation":{},"ISSN":["2475-7241"],"issn-type":[{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,4,4]]}}}