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However, relapse following therapy is frequently observed, and mechanisms of resistance remain ill-defined. Here, we perform single cell genomic characterization of longitudinal samples from a patient who relapsed after initial CAR T cell treatment with lack of response to retreatment. We report selection, following initial CAR T cell infusion, of a clone with biallelic loss of BCMA acquired by deletion of one allele and a mutation that creates an early stop codon on the second allele. This loss leads to lack of CAR T cell proliferation following the second infusion and is reflected by lack of soluble BCMA in patient serum. Our analysis suggests the need for careful detection of BCMA gene alterations in multiple myeloma cells from relapse following CAR T cell therapy.<\/jats:p>","DOI":"10.1038\/s41467-021-21177-5","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T16:31:35Z","timestamp":1612801895000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":393,"title":["Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9978-5682","authenticated-orcid":false,"given":"Mehmet Kemal","family":"Samur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-9742","authenticated-orcid":false,"given":"Mariateresa","family":"Fulciniti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-0562","authenticated-orcid":false,"given":"Anil","family":"Aktas Samur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0243-4040","authenticated-orcid":false,"given":"Abdul Hamid","family":"Bazarbachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-3569","authenticated-orcid":false,"given":"Yu-Tzu","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rao","family":"Prabhala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Sperling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Petrocca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Hege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9 Avet","family":"Loiseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6418-0886","authenticated-orcid":false,"given":"Kenneth C.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7344-9795","authenticated-orcid":false,"given":"Nikhil C.","family":"Munshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"21177_CR1","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1056\/NEJMoa1817226","volume":"380","author":"N Raje","year":"2019","unstructured":"Raje, N. et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl. J. Med. 380, 1726\u20131737 (2019).","journal-title":"N. Engl. J. Med."},{"key":"21177_CR2","doi-asserted-by":"publisher","first-page":"8503","DOI":"10.1200\/JCO.2020.38.15_suppl.8503","volume":"38","author":"NC Munshi","year":"2020","unstructured":"Munshi, N. C. et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): initial KarMMa results. J. Clin. Oncol. 38, 8503\u20138503 (2020).","journal-title":"J. Clin. Oncol."},{"key":"21177_CR3","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/s41375-020-0734-z","volume":"34","author":"N Shah","year":"2020","unstructured":"Shah, N., Chari, A., Scott, E., Mezzi, K. & Usmani, S. Z. B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches. 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N.C.M. is a consultant for BMS, Janssen, Oncopep, Amgen, Karyopharm, Legened, Abbvie, Takeda, and GSK, and on the board of directors and stock options Oncopep. T.C., K.H., and S.K. are employed by Bristol-Myers Squibb. F.P. is employed by Bluebird Bio. Other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"868"}}