Modeling Long-Term Progression-Free Survival in Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone

Daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) significantly improved progression-free survival (PFS) versus VRd in newly diagnosed multiple myeloma (NDMM) in transplant eligible (TE; PERSEUS) and transplant-ineligible (TIE; CEPHEUS) populations. Median PFS with DVRd has not been reached in either study. This analysis extrapolated PFS data from PERSEUS and CEPHEUS (TIE subgroup) to estimate long-term outcomes for DVRd. Following UK National Institute for Health and Care Excellence guidance on survival data extrapolation, seven parametric distributions were fitted to model PFS data. In PERSEUS (TE population), the projected median PFS range across distributions was 158-255 months versus 76-119 months and best-fit (exponential distribution) PFS estimates were 205 months (17.1 [range, 13.2-21.2] years, DVRd) versus 87 months (7.3 [range, 6.3-9.9] years, VRd). For CEPHEUS (TIE population), projected median PFS range across distributions was 96-118 months versus 52-54 months and best-fit estimates were 100 months (8.3 [range, 8.0-9.8] years, DVRd) versus 53 months (4.4 [range, 4.3-4.5] years, VRd). PFS projections were significantly longer with DVRd than VRd in TE (additional 118 months; 9.8 years) and TIE patients (additional 47 months; 3.9 years) across all seven distributions. These extrapolations reinforce the benefit of DVRd as standard of care in NDMM regardless of transplant eligibility.