biostudies-literaturePalomba MLCarson Family Charitable TrustEmerald FoundationCanada Club of New York, Annual Terry Fox Run for Cancer ResearchMemorial Sloan-Kettering Cancer CenterWilliam Lawrence and Blanche Hughes FoundationNCI NIH HHSNational Institutes of HealthMemorial Sloan-Kettering Cancer Center Experimental Therapeutics CenterNIH HHSe004128https://www.ebi.ac.uk/biostudies/studies/S-EPMC8852764biostudies-literatureUnknown10(2)<h4>Background</h4>Waldenström 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.<h4>Methods and results</h4>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 diJournal for immunotherapy of cancerCD19-directed chimeric antigen receptor T cell therapy in Waldenstrom macroglobulinemia: a preclinical model and initial clinical experience.PMC8852764K08CA241400-01U54 OD020355P30 CA008748K08 CA241400U54 OD020355-01R01 CA138738-05R01 CA138738Dogan ARiviere IPalomba MLBrentjens RJSethi SPark JHSenechal BMonette SSadelain MSmith ELRoshal MQualls DWang XfalseCD19-directed chimeric antigen receptor T cell therapy in Waldenstrom macroglobulinemia: a preclinical model and initial clinical experience.<h4>Background</h4>Waldenström 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.<h4>Methods and results</h4>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 di2022-01-01T00:00:00Z2022 Feb2026-06-07T03:18:56.717Z2025-04-06T13:56:13.17ZS-EPMC88527643517303010.1136/jitc-2021-004128