LCL/LBH synergistically circumvents microenvironment-driven resistance. (A) Ex vivo viability analysis of purified CD138⁺ patient MM cells in the context of patient stroma, collagen, and patient serum over 4 days with LCL161, panobinostat, or the combination (5 concentrations serially diluted threefold from 20 µM [LCL161], 50 nM [panobinostat]). Purple line is MM1.S cell line control at maximum concentration. (B) Quantitation of cell viability by area under the curves (AUC) of all 5 doses. (C) Quantification of synergy at 96 hours by AUC and median lethal dose (LD50). Responses greater than mathematically determined additivity are synergistic; values shown are increased experimental activity compared with expected additive response.¹⁸