Efficacy
346 patients were assigned to the daratumumab arm and 344 to the control group. During the first 9 cycles, 19.4% of patients discontinued treatment in the daratumumab arm, compared with 33.1% in the control group. Discontinuations were more frequent in the control group due to progressive disease (6.6% v 13.3%) and adverse events (4.9% v 9.3%).
The median PFS was not reached (NR) in the daratumumab group, compared with 18.1 months in the control group (p<0.001). 18 month PFS was 71.6% versus 50.2%. Superiority of daratumumab was seen across all subgroups, including poor-risk patients based on age, stage, and cytogenetics.r
Table 1: Prespecified subgroup analysis of progression-free survivalr
© NEJM 2018
Figure 1: Progression-free survivalr
© NEJM 2018
Overall response rate (ORR) was 90.9% in the daratumumab arm v 73.9% in the control group (p<0.001). Similarly, rates of complete response (CR) were higher in the experimental arm (42.6% v 24.4%, p<0.001).
Subsequent analysis at a median follow-up of 40.1 months has demonstrated a significant benefit in overall survival (OS) with the addition of daratumumab to VMP (HR 0.6, 95% CI 0.46-0.80, p = 0.0003).r Kaplan-Meier estimate of 3 year OS was 78% in the D-VMP arm and 67.9% in the VMP arm. There was a continued benefit with regard to PFS (HR 0.42, 95% CI 0.34-0.41, p < 0.0001). Median PFS was 36.4 months in the D-VMP group versus 19.3 months in the VMP arm.
A publication specifically focused on the frail population in this study demonstrated that non-frail patients had longer PFS and OS than frail patients.r Frail patients benefited from the addition of daratumumab to VMP in terms of PFS (32.9 vs 19.5 months, HR 0.51, p < 0.0001) and OS (3 year OS 71.4% vs 59%).
Figure 2: Survival analyses in the intention-to-treat populationr
© Lancet 2020