The addition of anti-CD38 monoclonal antibodies daratumumab to bortezomib, lenalidomide, and dexamethasone (D-VRd) has shown deeper responses in clinical trials. However, real-world data on D-VRd in patients with newly diagnosed MM (NDMM) remain limited in China. This study compared the efficacy and safety of D-VRd versus VRd focusing on high-risk subgroups. This was a prospective, multicenter, observational study conducted across six Chinese hospitals. We prospectively enrolled NDMM patients receiving first-line D-VRd between August 2020 and August 2024. A historical control cohort of NDMM patients treated with VRd was retrospectively included. High-risk criteria included cytogenetic abnormalities such as del(17p), t(4;14), t(14;16), or 1q21+, while ultra-high-risk (UHiR) defined as ≥ 2 HRCAs. The primary endpoint was progression-free survival (PFS). A multivariable Cox proportional hazards model was fitted, adjusting for key baseline characteristics. A total of 100 NDMM patients were prospectively enrolled in D-VRd group, the other 221 patients treated with VRd as a control cohort.The median follow-up time was 16.1 months in the D-VRd group and 40.2 months in the VRd group. For the primary endpoint, the 1-year PFS rate was significantly higher in the D-VRd group compared to the VRd group (92.0% vs. 84.5%; HR 0.58, 95% CI 0.36–0.92). Regarding secondary endpoints, the 1-year OS rate also showed improvement (99.0% vs. 97.0%; HR 0.30, 95% CI 0.12–0.72). Among patients with HRCAs, both 1-year PFS (91.5% vs. 80%; HR 0.41, 95% CI 0.23–0.73) and OS (100.0% vs. 92.2%; HR 0.27, 95% CI 0.10–0.77) were significantly improved with D-VRd. In UHiR patients, D-VRd also provided a significant PFS benefit (95.0% vs. 72.0%; HR 0.31, 95% CI 0.14–0.68). In cytogenetic-specific subgroup analyses, patients with 1q21+ (1-year PFS: 91% vs. 81%; HR 0.45, 95% CI 0.24–0.86) or del(17p) (1-year PFS: 86% vs. 63%; HR 0.28, 95% CI 0.11–0.74) derived significant benefit from D-VRd. Among transplant-ineligible patients, 1-year PFS showed a trend favoring D-VRd over VRd (88% vs. 81%; HR 0.56, 95% CI 0.32–0.99). In terms of safety, leukopenia was more frequent in the D-VRd group (22.9% vs. 7.4%), whereas peripheral neuropathy was less common (16.9% vs. 32.5%), with an overall manageable safety profile. This real-world multicenter study in China demonstrates that D-VRd, compared to VRd, provides superior efficacy with a manageable safety profile as frontline therapy for NDMM, particularly in high-risk patients.
Cheng et al. (Tue,) studied this question.