医学
多发性骨髓瘤
抗原
免疫学
等离子体电池
癌症研究
肿瘤科
内科学
作者
Ross S. Firestone,Nicholas D. Socci,Tala Shekarkhand,Menglei Zhu,Wei Qin,Malin Hultcrantz,Sham Mailankody,Carlyn Tan,Neha Korde,Alexander M. Lesokhin,Hani Hassoun,Urvi Shah,Kylee Maclachlan,Sridevi Rajeeve,Heather Landau,Michael Scordo,Gunjan L. Shah,Oscar Lahoud,Sergio Giralt,Kazunori Murata,Saad Z. Usmani,David J. Chung
出处
期刊:Blood
[American Society of Hematology]
日期:2024-05-10
被引量:2
标识
DOI:10.1182/blood.2023023557
摘要
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 x BCMA bispecific antibody (BsAb), 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 one of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from one 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.
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