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- W4313453663 abstract "The treatment of patients with relapsed or refractory lymphoid neoplasms represents a significant clinical challenge. Here, we identify the pro-survival BCL-2 protein family member MCL-1 as a resistance factor for the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma (NHL) cell lines and primary NHL samples. Mechanistically, we show that the antibody-drug conjugate polatuzumab vedotin promotes MCL-1 degradation via the ubiquitin/proteasome system. This targeted MCL-1 antagonism, when combined with venetoclax and the anti-CD20 antibodies obinutuzumab or rituximab, results in tumor regressions in preclinical NHL models, which are sustained even off-treatment. In a Phase Ib clinical trial (NCT02611323) of heavily pre-treated patients with relapsed or refractory NHL, 25/33 (76%) patients with follicular lymphoma and 5/17 (29%) patients with diffuse large B-cell lymphoma achieved complete or partial responses with an acceptable safety profile when treated with the recommended Phase II dose of polatuzumab vedotin in combination with venetoclax and an anti-CD20 antibody." @default.
- W4313453663 created "2023-01-06" @default.
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- W4313453663 date "2023-01-17" @default.
- W4313453663 modified "2023-10-17" @default.
- W4313453663 title "Targeting MCL‐1 and BCL‐2 with polatuzumab vedotin and venetoclax overcomes treatment resistance in R/R non‐Hodgkin lymphoma: Results from preclinical models and a Phase Ib study" @default.
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- W4313453663 doi "https://doi.org/10.1002/ajh.26809" @default.
- W4313453663 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36594167" @default.
- W4313453663 hasPublicationYear "2023" @default.
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