The multi-agent therapy “VDT-PACE” represents an established regimen in RRMM. Here, we report on our experience with a “modified VDT-PACE” incorporating new generation anti-MM agents daratumumab and carfilzomib (“Dara-KDT-P(A)CE”). We retrospectively analyzed 38 patients with RRMM treated with “Dara-KDT-P(A)CE”. The median age was 62 (rage 45-82) years, and the patients were heavily pretreated with a median of five (range 2-12) prior lines of therapy. Twenty-one (55%) patients suffered from penta-refractory MM. High-risk cytogenetics was present in 31 (81%) patients. The patients received a median of two (range 1-10) cycles of this therapy, and the ORR was 70%. Patients with penta-refractory MM and high-risk cytogenetics showed similar ORR of 65% and 79%, respectively. The median PFS and OS were 4.1 (95% CI 2.7-5.4) and 8.4 (95% CI 6.7-10.0) months, respectively. Patients with LDH>250 IU/l showed significantly shorter PFS in comparison with others patients (P=0.006). We used this regimen as bridging therapy prior to CAR T-cell infusion in four patients. In conclusion, “Dara-KDT-P(A)CE” is an effective salvage therapy for patients with heavily pretreated, multi-refractory, high-risk RRMM lacking alternative options.

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