{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:41:45Z","timestamp":1790991705875,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013560","name":"GBS\/CIDP Foundation International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Anti\u2010myelin\u2010associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety and maximum tolerated dose (MTD) in anti\u2010MAG neuropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase 1b, open\u2010label, single\u2010arm, dose\u2010finding trial was conducted from 2019 through 2022. The original design included a dose\u2010escalation\/extension phase followed by a dose\u2010expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25\u2009mg. The main outcome was the MTD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eleven patients enrolled (10 men), with a mean age of 67.6\u2009years (SD\u2009=\u20096.18, range 58\u201377\u2009years) and mean disease duration of 8.5\u2009years (SD\u2009=\u200910.9, range 1\u201340\u2009years). The study terminated early due to higher\u2010than\u2010expected non\u2010dose\u2010limiting toxicity venous thromboembolism (VTE) events. The calculated MTD was 25\u2009mg (posterior mean of toxicity probability was 0.01 with a 95% credible interval of 0.00, 0.06), but a recommended phase 2 dose of 15\u2009mg was advised. For secondary exploratory outcomes, only EQ\u20105D (\u22120.95, 95% CI \u22121.81 to \u22120.09) and total IgM (\u2212162\u2009mg\/dL, 95% CI \u2212298 to \u221226) showed signs of improvement by month 12.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Lenalidomide was associated with higher\u2010than\u2010expected VTE events in anti\u2010MAG neuropathy patients, despite a calculated MTD of 25\u2009mg. A recommended phase 2 dose of 15\u2009mg was advised. Lenalidomide did not improve disability or impairment at 12\u2009months, although this study was not powered for efficacy. The risks of long term lenalidomide may outweigh benefit for patients with anti\u2010MAG neuropathy. Any future efficacy study should address VTE risk, as current myeloma guidelines appear inadequate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>Lenalidomide in Anti\u2010MAG Neuropathy: Phase 1b Study, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> Identifier: NCT03701711, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03701711\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03701711<\/jats:ext-link>. First submitted October 10, 2018. First patient enrolled in January 2019.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16164","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T18:59:24Z","timestamp":1701197964000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lenalidomide in the treatment of anti\u2010myelin\u2010associated glycoprotein neuropathy: A phase 1 study to identify the maximum tolerated dose"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7793-6662","authenticated-orcid":false,"given":"Amro M.","family":"Stino","sequence":"first","affiliation":[{"name":"Department of Neurology, Division of Neuromuscular Medicine The University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Bumma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\u2010Oncology The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Biostatistics The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Davalos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuromuscular Medicine The University of Cincinnati Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuromuscular Medicine University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Christine","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\u2010Oncology The University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Pianko","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\u2010Oncology The University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Campagnaro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\u2010Oncology The University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Fierro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuromuscular Medicine The University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman","family":"Awad","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuromuscular Medicine The University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Murdock","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuromuscular Medicine The University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Pietrzak","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Loszanski","sequence":"additional","affiliation":[{"name":"Department of Pathology The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Kline","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Division of Public Health Sciences Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Efebera","sequence":"additional","affiliation":[{"name":"Department of Oncology Ohio Health  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakri","family":"Elsheikh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuromuscular Medicine The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-017-3024-4"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2016.1198257"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12190"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.08.001"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci58743"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-4598(199908)22:8<1030::aid-mus4>3.0.co;2-h"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577725"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002827.pub4"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.1069"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21577"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318296e92b"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.5692\/clinicalneurol.51.345"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2006.01.010"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01257.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-030544"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-378992"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.869329"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25709"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2011.05.019"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.12.023"},{"key":"e_1_2_11_22_1","volume-title":"IgM Multiple Myeloma: A Rare Subtype Highly Sensitive to Lenalidomide","author":"Moreno\u2010Aspitia A","year":"2008"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12455"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24175"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-16-0592"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23336"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14562"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2010.10.003"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070596"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070594"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.72.6679"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2028631"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13701"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14966"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-294405"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000507690"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26462"},{"key":"e_1_2_11_38_1","unstructured":"ZonderJ SchifferC.Multiple myeloma: prevention of venous thromboembolism in patients receiving immunomodulatory drugs (thalidomide lenalidomide and pomalidomide). UpToDate.2021."},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.168294"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2005.081547"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000001109"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2005.04.6474"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2016.1191013"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.16164","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T09:43:29Z","timestamp":1710755009000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.16164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/ene.16164"],"URL":"https:\/\/doi.org\/10.1111\/ene.16164","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,28]]},"assertion":[{"value":"2023-08-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e16164"}}