My-DST tracks drug resistance in MM patient primary samples from diagnosis through multiple relapses. (A) Heat map of single agent ex vivo drug testing in samples from patients with MM at single concentrations (PIs at 2.5 nM, IMiDs at 10 µM, Dex at 1 µM, and Cy at 3.75 µM). Samples with <80% of myeloma cells remaining after 48 hours of treatment were scored as sensitive to the drug (green), and samples with >80% of MM cells remaining after 48 hours of treatment were scored as resistant (red). Data represent the mean of 3 replicates. (B-C) Resistance to the PIs bortezomib and carfilzomib increased with prior LOT. (D-E) Resistance to the IMiDs lenalidomide and pomalidomide increased with prior LOT. (F-G) Cy and Dex sensitivity did not increase with prior LOT. (H-I) The ex vivo results among the PI and IMiD classes were highly correlated from sensitive to both (lower left) to resistant to both (upper right). However, differential results favoring one agent in each class (upper left and lower right) were observed. The straight lines and P values in panels B to G represent linear mixed model regression results, and the blue lines represent locally estimated scatterplot smoothing nonlinear curve fits, with gray borders indicating the 95% confidence intervals. The straight lines in panels H and I represent linear regression results, with the r and P values from Pearson’s correlations.