Prior clinical drug exposure results in decreased ex vivo myeloma drug sensitivity for PIs and IMiDs but no change in Dex or Cy sensitivity. (A) Ex vivo PI sensitivity measured by My-DST was significantly lower in bone marrow samples from patients who were relapsed or refractory to prior PI treatment. (B) IMiD sensitivity was also significantly lower in bone marrow samples from relapsed or refractory patients with a history of IMiD treatment. (C) No difference was observed in Cy sensitivity between samples from patients with prior clinical Cy exposure vs those who were Cy naive. (D) Dex sensitivity was also not different between samples from patients with prior clinical Dex exposure vs those who were Dex naive. Data points represent the means from each individual sample. Comparisons were made by using the Mann-Whitney U test (A) or 2-tailed Student t test (B-D). Pt, patient. *P < .05; ***P < .001.