(PA-429) Effectiveness of Daratumumab plus Bortezomib, Lenalidomide, and Dexamethasone (DVRd) Versus VRd as Frontline Treatment for Transplant-Eligible Newly Diagnosed Multiple Myeloma: A Chart Review Study

Introduction: Recently, a shift in the frontline (FL) treatment strategy for transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM) patients (pts) from a triplet (e.g., bortezomib [V], lenalidomide [R], and dexamethasone [d]) to a quadruplet regimen (e.g., daratumumab in combination with VRd [DVRd]) has been observed, driven by the pivotal PERSEUS and GRIFFIN trial data. While improved efficacy with DVRd over VRd has been established in these trials, there is a need to assess the comparative effectiveness in the real-world (RW) setting. The goal of this RW study was to compare the progression-free survival (PFS) among TE NDMM pts receiving DVRd plus DR or R maintenance (DVRd-DR/R) versus VRd plus R maintenance (VRd-R).

Methods: A retrospective, multi-center, chart review study was conducted at 10 clinical sites in the United States. Eligible TE adult pts with NDMM who initiated FL DVRd-DR/R or VRd-R between 1/1/2020 and 6/30/2022, were included. Pts were excluded if they previously received any multiple myeloma treatment for ≥30 days, participated in a multiple myeloma-related clinical trial, were treated for another invasive malignancy < 12 months prior to induction, or had amyloidosis at induction.

Comparability of baseline characteristics between cohorts was assessed using standardized differences (< 10%=balanced). PFS was assessed from time of FL therapy initiation until disease progression or death. Inverse probability of treatment weighting (IPTW) was used to balance difference in baseline characteristics between cohorts. A doubly-robust Cox proportional hazards model, additionally adjusting for baseline characteristics that remained imbalanced after IPTW, was used to estimate the hazard ratio (HR) of PFS in pts treated with DVRd-DR/R versus VRd-R.

Results: A total of 137 DVRd-DR/R (DR: 67 pts; R: 70 pts; median age: 63 years; female: 42%) and 86 VRd-R (median age: 65 years; female: 51%) pts were included. After IPTW, age, sex, race, ethnicity, disease stage, performance status, frailty, cytogenetic risk status (including 1q21 gain/amplification) were balanced. Remaining imbalanced characteristics, including region of residence, type of insurance, extramedullary disease, plasmacytomas, comorbidity score, and selected comorbidities, were included as covariates to the weighted regression. Median follow-up was 26.7 months for DVRd-DR/R cohort and 39.8 months for VRd-R cohort. Median PFS was not reached in either cohort. FL treatment with DVRd-DR/R led to a 63% reduction in risk of disease progression or death compared to VRd-R (HR=0.37, 95% confidence interval=0.17 to 0.80, p=0.006) as progression/death was observed in 11 (9%) DVRd-DR/R pts, and 32 (30%) VRd-R pts.

Conclusions: Consistent with the findings from the pivotal clinical trials, RW FL use of the daratumumab-based quadruplet regimen DVRd was associated with a significant PFS benefit compared to VRd among TE pts with NDMM, underscoring the superiority of DVRd as FL treatment for these pts.