Patients who were Dara refractory with ex vivo sensitivity to CD38 antibodies benefit from clinical re-treatment. (A) Schematic timeline of the acquisition of follow-up samples before re-treatment with an anti-CD38 monoclonal antibody. (B) Ex vivo drug sensitivity as determined by normalized viability with My-DST vs depth of clinical response at re-treatment. Drug sensitivity was defined as <80% normalized viability, and PR as a 50% change in paraprotein from baseline after initiating treatment. (C) Swimmers plot showing the clinical benefit of anti-CD38 antibody–based therapy in the 8 patients who were Dara refractory and received re-treatment. Orange bar indicates complete response (CR), light green bars indicate partial response(PR), and purple bars indicate stable disease (SD). (D) Among patients who were Dara refractory, there was no significant difference in the overall survival between those re-treated with anti-CD38 antibodies and those who were not re-treated. (E) The probability of survival between those patients who were Dara refractory treated with anti-BCMA CAR-T was significantly higher than that of those who were not. (F) The disease course for patient WCM3, shown by serum free light chain, who relapsed after prior daratumumab but was not refractory and achieved complete response to daratumumab-based treatment. Before re-treatment with anti-CD38 antibody–based treatment, a BM sample WCM3.1 was obtained 26 months after the last dose of daratumumab. (G) After re-treatment started, a BM sample WCM3.2 was obtained, in which the MM cell population drastically decreased and the CD38 level on MM cells decreased as well. Cemi, cemiplimab; D, daratumumab; d, dexamethasone; FN, false negative; FP, false positive; Iber, iberdomide; Isa, isatuximab; K, carfilzomib;; P, pomalidomide; R, lenalidomide; Re-tx, re-treatment; RR, relapsed and refractory; TN, true negative; TP, true positive; V, bortezomib.