Journal: Blood cancer journal
This study is a systematic review and meta-analysis evaluating frontline regimens for transplant-ineligible newly diagnosed multiple myeloma, focusing on anti-CD38–based quadruplets versus triplets.
Design and methods
- Included randomized clinical trials comparing:
- Quadruplets: daratumumab-VRd (D‑VRd), isatuximab-VRd (I‑VRd)
- Triplets: daratumumab-Rd (D‑Rd), VRd
- Total trials: 4 RCTs (n = 2,038)
- Methodology: Conducted according to Cochrane/PRISMA standards, with both network meta-analysis and reconstructed individual patient data analyses
- Primary outcomes: progression-free survival (PFS) and overall survival (OS); complete response (CR) also evaluated
Key efficacy results
- Estimated 60‑month PFS:
- D‑VRd: 66.4%
- I‑VRd: 63.2%
- D‑Rd: 51.9%
- VRd: 42.6%
- PFS comparisons:
- D‑VRd and I‑VRd vs D‑Rd: HR 0.65 (95% CI 0.48–0.87) and 0.68 (0.52–0.89)
- D‑VRd and I‑VRd vs VRd: HR 0.51 (0.39–0.67) and 0.53 (0.41–0.67)
- D‑Rd vs VRd: HR 0.77 (0.64–0.93; P = 0.007)
- Estimated 60‑month OS:
- D‑VRd: 72.8%
- I‑VRd: 72.2%
- D‑Rd: 67.1%
- VRd: 67.0%
- Pooled comparison (all quadruplets vs all triplets):
- PFS at 60 months: 64.7% vs 46.3%; HR 0.57 (0.47–0.69; P < 0.0001)
- OS at 60 months: 72.5% vs 67.1%; HR 0.78 (0.63–0.96; P = 0.02)
- OS benefit of quadruplets vs individual triplets:
- vs D‑Rd: HR 0.77 (0.60–0.98; P = 0.04)
- vs VRd: HR 0.77 (0.62–0.97; P = 0.02)
Network meta-analysis
- Quadruplet regimens ranked highest for complete response rate, PFS, and OS.
Clinical takeaway for practice
- Anti‑CD38–based quadruplet regimens (D‑VRd and I‑VRd) provide clinically meaningful and statistically significant improvements in both PFS and OS versus standard triplet backbones (D‑Rd and VRd) in transplant‑ineligible newly diagnosed multiple myeloma.
- These data support prioritizing anti‑CD38–containing quadruplets as preferred frontline therapy in this population, assuming tolerability and access.