{"title":"扎鲁替尼对CD79B突变、TCL1A高表达或MYC/BCL-2过度表达的非生殖中心B细胞样弥漫大B细胞淋巴瘤有效。","authors":"Yang Liu, Xiaopeng Ma, Xikun Wu, Xinfeng Hou, Wei Jin, Lina Fu, Xiaolei Xun, Yiling Yu, Zhirong Shen","doi":"10.1080/10428194.2024.2343779","DOIUrl":null,"url":null,"abstract":"<p><p>To evaluate the effects of gene mutations on Bruton tyrosine kinase inhibitor, zanubrutinib's effectiveness in patients with diffuse large B-cell lymphoma (DLBCL), we examined pooled data from four single-arm studies (BGB-3111-AU-003 [NCT02343120], BGB-3111-207 [NCT03145064], BGB-3111_GA101_Study_001 [NCT02569476], BGB-3111-213 [NCT03520920]; <i>n</i> = 121). Objective response rate (ORR) was higher, though not statistically significant, in patients with activated B-cell-like (ABC)- and unclassified DLBCL (42.9% [21/49]) versus those with germinal-center B-cell-like DLBCL (14.3% [1/7]; <i>p</i> = 0.15). Patients with <i>CD79B</i> mutations had better ORR (60%) versus patients with wild-type alleles (25.9%, <i>p</i> < 0.01). Higher <i>TCL1A</i> expression correlated with better zanubrutinib response (<i>p</i> = 0.03), longer progression-free survival (<i>p</i> = 0.01), and longer overall survival (<i>p</i> = 0.12). <i>TCL1A</i> expression was higher in ABC-DLBCL (<i>p</i> < 0.001) and <i>MYD88</i>/<i>CD79B</i>-mutated subtypes (<i>p</i> < 0.0001). Eighteen patients with high MYC/BCL-2 expression responded better to zanubrutinib (ORR = 61 <i>vs.</i> 29%, <i>p</i> = 0.02). Our results support assessing <i>CD79B</i> mutations, co-expressor DLBCL, and <i>TCL1A</i> expression status to identify patients with DLBCL who will benefit from zanubrutinib.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Zanubrutinib is effective in non-germinal-center B-cell-like diffuse large B-cell lymphoma with mutated <i>CD79B</i>, high <i>TCL1A</i> expression, or over- expressed MYC/BCL-2.\",\"authors\":\"Yang Liu, Xiaopeng Ma, Xikun Wu, Xinfeng Hou, Wei Jin, Lina Fu, Xiaolei Xun, Yiling Yu, Zhirong Shen\",\"doi\":\"10.1080/10428194.2024.2343779\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>To evaluate the effects of gene mutations on Bruton tyrosine kinase inhibitor, zanubrutinib's effectiveness in patients with diffuse large B-cell lymphoma (DLBCL), we examined pooled data from four single-arm studies (BGB-3111-AU-003 [NCT02343120], BGB-3111-207 [NCT03145064], BGB-3111_GA101_Study_001 [NCT02569476], BGB-3111-213 [NCT03520920]; <i>n</i> = 121). Objective response rate (ORR) was higher, though not statistically significant, in patients with activated B-cell-like (ABC)- and unclassified DLBCL (42.9% [21/49]) versus those with germinal-center B-cell-like DLBCL (14.3% [1/7]; <i>p</i> = 0.15). Patients with <i>CD79B</i> mutations had better ORR (60%) versus patients with wild-type alleles (25.9%, <i>p</i> < 0.01). Higher <i>TCL1A</i> expression correlated with better zanubrutinib response (<i>p</i> = 0.03), longer progression-free survival (<i>p</i> = 0.01), and longer overall survival (<i>p</i> = 0.12). <i>TCL1A</i> expression was higher in ABC-DLBCL (<i>p</i> < 0.001) and <i>MYD88</i>/<i>CD79B</i>-mutated subtypes (<i>p</i> < 0.0001). Eighteen patients with high MYC/BCL-2 expression responded better to zanubrutinib (ORR = 61 <i>vs.</i> 29%, <i>p</i> = 0.02). Our results support assessing <i>CD79B</i> mutations, co-expressor DLBCL, and <i>TCL1A</i> expression status to identify patients with DLBCL who will benefit from zanubrutinib.</p>\",\"PeriodicalId\":18047,\"journal\":{\"name\":\"Leukemia & Lymphoma\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia & Lymphoma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/10428194.2024.2343779\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia & Lymphoma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10428194.2024.2343779","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/22 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Zanubrutinib is effective in non-germinal-center B-cell-like diffuse large B-cell lymphoma with mutated CD79B, high TCL1A expression, or over- expressed MYC/BCL-2.
To evaluate the effects of gene mutations on Bruton tyrosine kinase inhibitor, zanubrutinib's effectiveness in patients with diffuse large B-cell lymphoma (DLBCL), we examined pooled data from four single-arm studies (BGB-3111-AU-003 [NCT02343120], BGB-3111-207 [NCT03145064], BGB-3111_GA101_Study_001 [NCT02569476], BGB-3111-213 [NCT03520920]; n = 121). Objective response rate (ORR) was higher, though not statistically significant, in patients with activated B-cell-like (ABC)- and unclassified DLBCL (42.9% [21/49]) versus those with germinal-center B-cell-like DLBCL (14.3% [1/7]; p = 0.15). Patients with CD79B mutations had better ORR (60%) versus patients with wild-type alleles (25.9%, p < 0.01). Higher TCL1A expression correlated with better zanubrutinib response (p = 0.03), longer progression-free survival (p = 0.01), and longer overall survival (p = 0.12). TCL1A expression was higher in ABC-DLBCL (p < 0.001) and MYD88/CD79B-mutated subtypes (p < 0.0001). Eighteen patients with high MYC/BCL-2 expression responded better to zanubrutinib (ORR = 61 vs. 29%, p = 0.02). Our results support assessing CD79B mutations, co-expressor DLBCL, and TCL1A expression status to identify patients with DLBCL who will benefit from zanubrutinib.
期刊介绍:
Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor