{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:35:37Z","timestamp":1790825737326,"version":"4.1.0"},"reference-count":25,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Canada Club of New York, Annual Terry Fox Run for Cancer Research"},{"DOI":"10.13039\/100007052","name":"Memorial Sloan-Kettering Cancer Center","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100007052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007052","name":"Memorial Sloan-Kettering Cancer Center","doi-asserted-by":"publisher","award":["U54 OD020355-01"],"award-info":[{"award-number":["U54 OD020355-01"]}],"id":[{"id":"10.13039\/100007052","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Memorial Sloan-Kettering Cancer Center Experimental Therapeutics Center"},{"DOI":"10.13039\/501100012647","name":"William Lawrence and Blanche Hughes Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012647","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Carson Family Charitable Trust"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08CA241400-01"],"award-info":[{"award-number":["K08CA241400-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA138738-05"],"award-info":[{"award-number":["R01 CA138738-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014894","name":"Emerald Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,1,1]]},"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Waldenstr\u00f6m macroglobulinemia (WM) is an incurable disease and, while treatable, can develop resistance to available therapies and be fatal. Chimeric antigen receptor (CAR) T cell therapy directed against the CD19 antigen has demonstrated efficacy in relapsed or refractory B lymphoid malignancies, and is now approved for B cell acute lymphoblastic leukemia and certain B cell lymphomas. However, CAR T therapy has not been evaluated for use in WM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We performed preclinical studies demonstrating CAR T cell activity against WM cells in vitro, and developed an in vivo murine model of WM which demonstrated prolonged survival with use of CAR T therapy. We then report the first three patients with multiply relapsed and refractory WM treated for their disease with CD19-directed CAR T cells on clinical trials. Treatment was well tolerated, and observed toxicities were consistent with those seen in CAR T treatment for other diseases, and no grade 3 or higher cytokine release syndrome or neurotoxicity events occurred. All three patients attained at least a clinical response to treatment, including one minimal residual disease-negative complete response, though all three eventually developed recurrent disease between 3 and 26 months after initial treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This report summarizes preclinical and clinical activity of CD19-directed CAR T therapy in WM, demonstrating early tolerability and efficacy in patients with WM, and representing a possible treatment option in patients with heavily pretreated and relapsed or refractory WM. Larger studies evaluating CAR T therapy in WM are warranted, along with further evaluation into mechanisms of resistance to CAR T therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2021-004128","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T11:16:38Z","timestamp":1645010198000},"page":"e004128","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["CD19-directed chimeric antigen receptor T cell therapy in Waldenstr\u00f6m macroglobulinemia: a preclinical model and initial clinical experience"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct00466531","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03085173","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00466531","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03085173","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00466531","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00466531","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03085173","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03085173","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00466531","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03085173","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00466531","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03085173","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"M Lia","family":"Palomba","sequence":"first","affiliation":[{"name":"Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5297-9685","authenticated-orcid":false,"given":"David","family":"Qualls","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Monette","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenon","family":"Sethi","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center Department of Pathology, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Dogan","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center Department of Pathology, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Roshal","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center Department of Pathology, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Senechal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cell Therapy, Memorial Sloan Kettering Cancer Center, New York, New York, USA"},{"name":"Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cell Therapy, Memorial Sloan Kettering Cancer Center, New York, New York, USA"},{"name":"Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Rivi\u00e8re","sequence":"additional","affiliation":[{"name":"Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Sadelain","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cell Therapy, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renier J","family":"Brentjens","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cell Therapy, Memorial Sloan Kettering Cancer Center, New York, New York, USA"},{"name":"Department of Medicine, Division of Leukemia, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae H","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cell Therapy, Memorial Sloan Kettering Cancer Center, New York, New York, USA"},{"name":"Department of Medicine, Division of Leukemia, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0296-7587","authenticated-orcid":false,"given":"Eric L","family":"Smith","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"2025100304300204000_10.2.e004128.1","unstructured":"Swerdlow SH , Campo E , Harris NL . WHO classification of tumours of haematopoietic and lymphoid tissues. revised 4t. Lyon, France: IARC Press, International Agency for Research on Cancer, 2017."},{"key":"2025100304300204000_10.2.e004128.2","doi-asserted-by":"crossref","first-page":"e827","DOI":"10.1016\/S2352-3026(20)30224-6","article-title":"Consensus treatment recommendations from the tenth International workshop for Waldenstr\u00f6m macroglobulinaemia","volume":"7","author":"Castillo","year":"2020","journal-title":"Lancet Haematol"},{"key":"2025100304300204000_10.2.e004128.3","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1111\/bjh.16492","article-title":"Cause-specific mortality in individuals with lymphoplasmacytic lymphoma\/Waldenstr\u00f6m macroglobulinaemia, 2000-2016","volume":"189","author":"Dalal","year":"2020","journal-title":"Br J Haematol"},{"key":"2025100304300204000_10.2.e004128.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866"},{"key":"2025100304300204000_10.2.e004128.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1914347"},{"key":"2025100304300204000_10.2.e004128.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31366-0"},{"key":"2025100304300204000_10.2.e004128.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30864-7"},{"key":"2025100304300204000_10.2.e004128.8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood-2020-140491","article-title":"Updated follow-up of patients with relapsed\/refractory chronic lymphocytic leukemia\/small lymphocytic lymphoma treated with lisocabtagene maraleucel in the phase 1 monotherapy cohort of TRANSCEND CLL 004, including high-risk and ibrutinib-treated patients","volume":"136","author":"Siddiqi","year":"2020","journal-title":"Blood"},{"key":"2025100304300204000_10.2.e004128.9","first-page":"40","article-title":"Primary analysis of Zuma-5: a phase 2 study of Axicabtagene Ciloleucel (Axi-Cel) in patients with relapsed\/refractory (R\/R) indolent non-Hodgkin lymphoma (iNHL)","volume":"136","author":"Jacobson","year":"2020","journal-title":"Blood"},{"key":"2025100304300204000_10.2.e004128.10","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.ymthe.2018.03.016","article-title":"Development and evaluation of an optimal human single-chain variable fragment-derived BCMA-Targeted CAR T cell vector","volume":"26","author":"Smith","year":"2018","journal-title":"Mol Ther"},{"key":"2025100304300204000_10.2.e004128.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.05.022"},{"key":"2025100304300204000_10.2.e004128.12","doi-asserted-by":"crossref","unstructured":"Geyer MB , Rivi\u00e8re I , S\u00e9n\u00e9chal B , et al . Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed\/refractory CLL. JCI Insight 2019;4.doi:10.1172\/jci.insight.122627","DOI":"10.1172\/jci.insight.122627"},{"key":"2025100304300204000_10.2.e004128.13","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2018-99-117737","article-title":"A Phase I First-in-Human Clinical Trial of CD19-Targeted 19-28z\/4-1BBL \"Armored\" CAR T Cells in Patients with Relapsed or Refractory NHL and CLL Including Richter\u2019s Transformation","volume":"132","author":"Park","year":"2018","journal-title":"Blood"},{"key":"2025100304300204000_10.2.e004128.14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709919"},{"key":"2025100304300204000_10.2.e004128.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2016.10.020"},{"key":"2025100304300204000_10.2.e004128.16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817226"},{"key":"2025100304300204000_10.2.e004128.17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/10428194.2019.1665668","article-title":"Chimeric antigen receptor T cells for treatment of transformed Waldenstr\u00f6m macroglobulinemia","volume":"61","author":"Bansal","year":"2020","journal-title":"Leuk Lymphoma"},{"key":"2025100304300204000_10.2.e004128.18","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2005.n.007"},{"key":"2025100304300204000_10.2.e004128.19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024850"},{"key":"2025100304300204000_10.2.e004128.20","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-20-0020"},{"key":"2025100304300204000_10.2.e004128.21","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1038\/s41591-020-1081-3","article-title":"Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial","volume":"26","author":"Shah","year":"2020","journal-title":"Nat Med"},{"key":"2025100304300204000_10.2.e004128.22","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2020.38.15_suppl.8001","article-title":"Phase I Alexander study of AUTO3, the first CD19\/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed\/refractory (r\/r) DLBCL","volume":"38","author":"Osborne","year":"2020","journal-title":"JCO"},{"key":"2025100304300204000_10.2.e004128.23","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1314"},{"key":"2025100304300204000_10.2.e004128.24","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1527"},{"key":"2025100304300204000_10.2.e004128.25","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1182\/blood.2019002936","article-title":"Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure","volume":"135","author":"Gauthier","year":"2020","journal-title":"Blood"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2021-004128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T11:30:13Z","timestamp":1759491013000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2021-004128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,16]]},"published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1136\/jitc-2021-004128"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2021-004128","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2]]}}}