MM cell sensitivity to MCL-1i treatment is highly variable, and combination of MCL-1i with other BH3 mimetics synergistically induces cell death. (A) Specific apoptosis induced in MM PCs (n = 47), distinguished by their CD38⁺ phenotype, after 24 hours of treatment with the indicated concentrations of MCL-1i S63845. (B) Specific apoptosis induced in MM PCs (n = 47) after combination of MCL-1i treatment (at indicated concentrations) with 100 nM of BCL-2i or BCL-XLi. Black lines indicate average values. (C) Representative example of flow cytometric analysis of apoptosis induction in CD38⁺ (MM) cells after 24 hours of treatment with the indicated BH3 mimetics. Outlined areas indicate the populations of viable (DiOC6⁺/TO-PRO-3⁻) cells. (D) Linear regression analysis between specific apoptosis of MM samples (n = 6) cultured on MS-5 cells and MSCs, after treatment with indicated concentrations of MCL-1i (upper) or BCL-2i (lower). Tables show all coefficients of determination (R² values) for MS-5 and other culture systems, after treatment with MCL-1i or BCL-2i. *P < .05, **P < .01, ***P < .001.