Efficacy
286 patients were randomised to receive daratumumab, with 283 patients assigned to the control group. Median age was 65 years in each arm; 63.3% of patients had undergone at least one stem cell transplant. 19.2% of patients had received at least 3 prior lines of therapy; 27.4% of patients had disease refractory to the last line of therapy.r
In the initial analysis, at a median follow-up of 13.5 months, the median PFS was not reached in the daratumumab arm, compared with 18.4 months in the control group. 12-month PFS was 83.2% in the daratumumab arm versus 60.1% in the control group (hazard ratio (HR) 0.37, p<0.001). Overall response rate (ORR) was higher in the daratumumab arm (92.9% v 76.4%, p<0.001), as was the rate of complete response (CR) (43.1% v 19.2%, p<0.001). Patients with deeper responses had longer PFS.r
In the extended follow-up analysis published in 2020,r after a median follow-up of 44.3 months, DRd prolonged PFS (median 44.5 months versus 17.5 months; HR 0.44; 95% CI, 0.35-0.55; p<0.0001). The PFS benefit was maintained across all subgroups. DRd demonstrated higher ORR (92/9 versus 76.4%; p<0.0001) and deeper responses including CR or better (56.6 versus 23.2%; p<0.0001) and MRD negativity (10-5; 30.4 versus 5.3%; p<0.0001). Median time to next therapy was prolonged with DRd (50.6 versus 23.1 months; HR 0.39; 95% CI, 0.31-0.50; p<0.0001).
Figure 1. Progression-free survival (PFS) in (a) the intent-to-treat (ITT) population; and in patients with (b) one prior line of therapy, (c) responses of CR or better, (d) prior lenalidomide exposure, and (e) refractoriness to bortezomib.r
© Leukaemia 2020
In the final OS analysis published in 2023,r after a follow-up of >6.5 years was reported with a significant OS benefit observed in the experimental arm (DRd) at a median follow-up of 79.7 months (HR 0.73; 95% CI 0.58 to 0.91, p=0.0044). The median OS was 67.6 months for DRd compared to 51.8 months for Rd. The benefit was maintained across all subgroups including patients age ≥65 years, patients with 1-3 prior lines of therapy, ISS III disease, high-risk cytogenetic abnormalities and refractoriness to last prior line of therapy or proteasome inhibitor. Furthermore, PFS on subsequent line of therapy (PFS2) was significantly prolonged in the DRd arm compared to the Rd arm.
Figure 2. Kaplan-Meier estimates of (A) overall survival (OS) and (B) progression-free survival on the subsequent line of therapy (PFS2) in the ITT populationr
© J Clin Oncol 2023