Nelfinavir interacts with mitochondrial VDACs and disrupts oxidative phosphorylation in proteasome inhibitor resistant myeloma

Besse, A.; Besse, L.; Stolze, S.C.; Zaal, E.; Berkers, C.; Everts, B.; ... ; Driessen, C. (2019)

Article / Letter to editor

Venetoclax is an oral BCL2 inhibitor undergoing investigation for use in relapsed or refractory multiple myeloma (RRMM), particularly in combination with proteasome inhibitors (VPI)[1,2]. An interim analysis of a current phase 2 trial of venetoclax with carfilzomib in RRMM demonstrated an overall response rate of 78% with a very good partial response rate of 56%[3,4]. However, a separate ongoing phase 3 trial of venetoclax with bortezomib found a decrease in overall survival due to increased fatal infections in the venetoclax arm compared to placebo. Better describing these infections may give insight into the pathophysiology and prove useful in mitigating strategies for use with VPI therapy in RRMM.

• Drug resistance
• Metabolism
• Nelfinavir

• All authors: Besse, A.; Besse, L.; Stolze, S.C.; Zaal, E.; Berkers, C.; Everts, B.; Phuyal, S.; Kraus, M.; Sobh, A.; Silzle, T.; Vulpe, C.; Farhan, H.; Overkleeft, H.S.; Driessen, C.
• Date: 2019-10-31
• Volume: 19
• Issue: 10
• Pages: E125 - E126
• DOI: doi:10.1016/j.clml.2019.09.207
• Link: https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(19)31594-0/abstract