{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:54:42Z","timestamp":1789012482915,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Venetoclax is effective in relapsed patients with mantle cell lymphoma (MCL). Mechanisms of resistance to venetoclax in MCL are poorly understood. We describe the clinical outcomes and genomic characteristics of 24 multiply relapsed patients (median of five prior lines of therapy) who received venetoclax\u2010based therapies; 67% had progressed on BTK inhibitors (BTKi) and 54% had blastoid or pleomorphic histology. Median follow up after venetoclax treatment was 17\u2009months. The overall response rate was 50% and complete response (CR) rate was 21%, 16 patients had progressed and 15 died. The median progression free, overall and post venetoclax survival were 8, 13.5 and 7.3 months respectively. Whole\u2010exome sequencing (WES) was performed on samples collected from seven patients (including five pairs; before starting venetoclax and after progression on venetoclax). The <jats:italic>SMARCA4<\/jats:italic> and <jats:italic>BCL2<\/jats:italic> alterations were noted only after progression, while <jats:italic>TP53, CDKN2A, KMT2D, CELSR3, CCND1, NOTCH2<\/jats:italic> and <jats:italic>ATM<\/jats:italic> were altered 2\u20104\u2010fold more frequently after progression. In two patients with serial samples, we demonstrated clonal evolution of novel <jats:italic>SMARCA4<\/jats:italic> and <jats:italic>KMT2C\/D<\/jats:italic> mutations at progression. Mutation dynamics in venetoclax resistant MCL is demonstrated. Our data indicates that venetoclax resistance in MCL is predominantly associated with non\u2010BCL2 gene mutations. Further studies are ongoing in MCL patients to evaluate the efficacy of venetoclax in combination with other agents and understand the biology of venetoclax resistance in MCL.<\/jats:p>","DOI":"10.1002\/ajh.25796","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T13:05:12Z","timestamp":1585832712000},"page":"623-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (<scp>MCL<\/scp>) \u2010 outcomes and mutation profile from venetoclax resistant <scp>MCL<\/scp> patients"],"prefix":"10.1002","volume":"95","author":[{"given":"Shuangtao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine The University of Texas MD Anderson Cancer Center  Houston Texas 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