Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma.

Autor:	Firestone RS; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Socci ND; Department of Engineering and Bioinformatics, Memorial Sloan Kettering Cancer Center, New York, NY., Shekarkhand T; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Zhu M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Qin WG; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Hultcrantz M; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Mailankody S; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Tan CR; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Korde N; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Lesokhin AM; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Hassoun H; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Shah U; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Maclachlan KH; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY., Rajeeve S; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Landau HJ; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Scordo M; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Shah GL; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Lahoud OB; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Giralt S; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Murata K; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Usmani SZ; Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Chung DJ; Department of Medicine, Weill Cornell Medical College, New York, NY.; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Jul 25; Vol. 144 (4), pp. 402-407.
DOI:	10.1182/blood.2023023557
Abstrakt:	Abstract: B-cell maturation antigen (BCMA)-targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined. We analyzed outcomes for 72 RRMM patients treated with teclistamab, a CD3 × BCMA bispecific antibody, 42% (30/72) of whom had prior BCMA-directed therapy exposure. Malignant plasma cell BCMA expression was present in all BCMA therapy-naïve patients. Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and 1 of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from 1 patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu