Fig. 6: Selinexor sensitivity in 113 MM ex vivo primary patient samples.
From: “Direct to Drug” screening as a precision medicine tool in multiple myeloma
a Heatmap showing cellular efficacy of single agent selinexor response following a 24 h drug exposure in 113 primary patient samples rank-ordered by drug sensitivity, associated to clinical data including diagnosis, MM disease status, mSMART 3.0 risk group classification for active MM, flow cytometry S-Phase analysis, FISH cytogenetics, and TP53 and ZFHX4 mutation status. Missing data are colored in grey. b–i Plots of selinexor differential sensitivity by class showing: b increased ex vivo sensitivity to selinexor associated to samples from patients with MM (n = 99; median AUC 0.4198) when compared to patients with SMM (n = 14; median AUC 0.6029) (Mann–Whitney test; p < 0.0001); c a trend towards statistical significance of increased ex vivo sensitivity to selinexor associated to relapsed MM (1st and ≥2 relapsed groups combined; n = 64; median AUC 0.3844) when compared to newly diagnosed MM (n = 35; median AUC 0.4570) (Mann–Whitney test; p = 0.0647) and a significant increase in sensitivity in patients at a second or further relapse (n = 48; median AUC 0.3518) when compared to the first relapse (n = 16; median AUC 0.4974) (Mann–Whitney test; p = 0.0046); d increased ex vivo sensitivity to selinexor associated to high mSMART risk (n = 60; median AUC 0.3804) when compared to standard risk (n = 36; median AUC 0.4573) (Mann–Whitney test; p = 0.0289); e increased ex vivo sensitivity to selinexor associated to high plasma cell S-Phase (n = 31; median AUC 0.3840) when compared to low S-Phase (n = 65; median AUC 0.4738) (Mann–Whitney test; p = 0.0305); f a trend towards statistical significance of increased ex vivo sensitivity to selinexor associated to samples harboring t(4;14) (n = 11; median AUC 0.2796) when compared to samples lacking the translocation (n = 99; median AUC 0.4465) (Mann–Whitney test; p = 0.0676) or g in samples presenting a 17p deletion (n = 17; median AUC 0.3542) when compared to samples without the deletion (n = 93; median AUC 0.4559) (Mann–Whitney test; p = 0.0883); h increased ex vivo sensitivity to selinexor associated to samples with TP53 mutations (n = 9; median AUC 0.2814) when compared to samples without the mutation (n = 64; median AUC 0.4480) (Mann–Whitney test; p = 0.0212); i increased ex vivo sensitivity to selinexor associated to ZFHX4 mutations (n = 10; median AUC 0.2527) when compared to samples without the mutation (n = 63; median AUC 0.4475) (Mann–Whitney test; p = 0.0197).
