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
dc.contributor.author | Lasater, Elisabeth A. | |
dc.contributor.author | Amin, Dhara N. | |
dc.contributor.author | Bannerji, Rajat | |
dc.contributor.author | Mali, Raghuveer Singh | |
dc.contributor.author | Barrett, Kathy | |
dc.contributor.author | Rys, Ryan N. | |
dc.contributor.author | Oeh, Jason | |
dc.contributor.author | Lin, Eva | |
dc.contributor.author | Sterne-Weiler, Tim | |
dc.contributor.author | Ingalla, Ellen Rei | |
dc.contributor.author | Go, MaryAnn | |
dc.contributor.author | Yu, Shang-Fan | |
dc.contributor.author | Krem, Maxwell M. | |
dc.contributor.author | Arthur, Chris | |
dc.contributor.author | Hahn, Uwe | |
dc.contributor.author | Johnston, Anna | |
dc.contributor.author | Karur, Vinit | |
dc.contributor.author | Khan, Nadia | |
dc.contributor.author | Marlton, Paula | |
dc.contributor.author | Phillips, Tycel | |
dc.contributor.author | Gritti, Giuseppe | |
dc.contributor.author | Seymour, John F. | |
dc.contributor.author | Tani, Monica | |
dc.contributor.author | Yuen, Sam | |
dc.contributor.author | Martin, Scott | |
dc.contributor.author | Chang, Matthew T. | |
dc.contributor.author | Rose, Christopher M. | |
dc.contributor.author | Pham, Victoria C. | |
dc.contributor.author | Polson, Andrew G. | |
dc.contributor.author | Chang, YiMeng | |
dc.contributor.author | Wever, Claudia | |
dc.contributor.author | Johnson, Nathalie A. | |
dc.contributor.author | Jiang, Yanwen | |
dc.contributor.author | Hirata, Jamie | |
dc.contributor.author | Sampath, Deepak | |
dc.contributor.author | Musick, Lisa | |
dc.contributor.author | Flowers, Christopher R. | |
dc.contributor.author | Wertz, Ingrid E. | |
dc.date.accessioned | 2023-03-03T21:10:06Z | |
dc.date.available | 2024-04-03 16:10:03 | en |
dc.date.available | 2023-03-03T21:10:06Z | |
dc.date.issued | 2023-03 | |
dc.identifier.citation | Lasater, Elisabeth A.; Amin, Dhara N.; Bannerji, Rajat; Mali, Raghuveer Singh; Barrett, Kathy; Rys, Ryan N.; Oeh, Jason; Lin, Eva; Sterne-Weiler, Tim ; Ingalla, Ellen Rei; Go, MaryAnn; Yu, Shang-Fan ; Krem, Maxwell M.; Arthur, Chris; Hahn, Uwe; Johnston, Anna; Karur, Vinit; Khan, Nadia; Marlton, Paula; Phillips, Tycel; Gritti, Giuseppe; Seymour, John F.; Tani, Monica; Yuen, Sam; Martin, Scott; Chang, Matthew T.; Rose, Christopher M.; Pham, Victoria C.; Polson, Andrew G.; Chang, YiMeng; Wever, Claudia; Johnson, Nathalie A.; Jiang, Yanwen; Hirata, Jamie; Sampath, Deepak; Musick, Lisa; Flowers, Christopher R.; Wertz, Ingrid E. (2023). "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." American Journal of Hematology 98(3): 449-463. | |
dc.identifier.issn | 0361-8609 | |
dc.identifier.issn | 1096-8652 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/175920 | |
dc.description.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. | |
dc.publisher | John Wiley & Sons, Inc. | |
dc.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 | |
dc.type | Article | |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Oncology and Hematology | |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | |
dc.subject.hlbtoplevel | Science | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/175920/1/ajh26809_am.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/175920/2/ajh26809.pdf | |
dc.identifier.doi | 10.1002/ajh.26809 | |
dc.identifier.source | American Journal of Hematology | |
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