FIGURE 1 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors

Statins significantly improve responses in a retrospective analysis of venetoclax clinical trials in R/R multiple myeloma. Results of patients with R/R multiple myeloma from venetoclax clinical trials receiving the standard therapy of Dex and a proteasome inhibitor (bortezomib for the phase Ib trial (NCT01794507 also known as M12-901) and carfilzomib for the ongoing phase II trial (NCT02899052 also known as M15-538) were pooled for post hoc analysis of background statin use on responses to therapy. A, Univariate analysis of the pooled trials assessing background statin use on response to therapy identified a significant difference in the proportion of subjects achieving sCR that is appreciated in each individual study (***, P < 0.001). B, No patient on statins experienced progressive disease (PD) in either individual study, resulting in a significant difference in the pooled analysis (*, P < 0.05). C, Multivariate analysis to evaluate known independent variables that affect patient outcomes, including prior lines of therapy, cytogenetic risk, and t(11;14) status in relation to statin use on patient responses. Statin use trended closer to support association with CR or better when accounting for prior lines of therapy, while t(11;14) and cytogenetic risk had no association with CR or better. No high-risk patients achieved sCR, thus cytogenetic risk was dropped from multivariate analysis of sCR. Neither prior lines of therapy nor t(11;14) status were associated with sCR, while statin use was strongly associated with increased rates of sCR (**, P < 0.01).