P-115: Progression-Free Survival of Daratumumab vs. Bortezomib Triplet Combination with Lenalidomide and Dexamethasone in Transplant Ineligible Newly Diagnosed Multiple Myeloma Patients: A Chart Review Study

Introduction: Daratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are the only guideline recommended preferred regimens for the treatment of transplant ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Both DRd and VRd have demonstrated superior efficacy vs. Rd in the MAIA and SWOG S0777 trials, respectively, but there is no head-to-head (H2H) clinical trial comparing their efficacy. Differing populations in MAIA (TIE [99% patients aged ≥65 years]) and S0777 (transplant not-intended [43% patients aged ≥65 years]) trials, make a naïve unadjusted comparison of outcomes across these trials challenging and biased. The current TAURUS chart review study is the first H2H study comparing the progression-free survival (PFS) among TIE NDMM patients treated with DRd or VRd as first-line of therapy (1L) in similar clinical settings.

Methods: A multicenter chart review study was conducted at 9 academic and community cancer centers across the US. Patients ≥65 years with NDMM, considered TIE by the treating physician were included if they initiated DRd/VRd as 1L between January 2019 and September 2021. The sample included all eligible patients treated with DRd and a random sample of VRd patients.

PFS was defined as the time from DRd/VRd initiation until disease progression (per physician assessment and guided by the IMWG criteria) or death. Comparability of baseline characteristics between cohorts was assessed using standardized differences (std.diff.). Characteristics with std.diff. ≥10% were considered imbalanced. The Inverse Probability of Treatment Weighting (IPTW) method was used to balance characteristics. A doubly robust Cox regression model, adjusting for clinically relevant baseline characteristics which remained imbalanced after weighting, was used to compare PFS between cohorts.

Results: Charts of 99 DRd and 78 VRd patients were abstracted. After weighting (DRd weighted n=91, VRd weighted n=87), mean age of patients (DRd: 76.2 years, VRd: 75.9 years) and gender distribution (female; DRd: 51%, VRd: 52%) were similar between cohorts. ECOG categories, 1q21 gain/amplification, and other high-risk cytogenetics (t-[4;14], t-[14;16], del [17p]) were also well balanced. Small differences were observed in year of index date and ISS staging, which were added as regressors to the Cox model. At data cut-off, 13 DRd (14.5%) and 24 VRd (28.2%) patients experienced disease progression or death. Patients treated with 1L DRd had a 65% lower risk of disease progression or death compared to 1L VRd (adjusted hazard ratio=0.35, 95% CI: 0.17-0.73, p< 0.01).

Conclusions: DRd is associated with a significantly lower risk of disease progression or death compared to VRd as 1L treatment for TIE NDMM patients. Results from the current TAURUS chart review study could help inform the selection of optimal 1L treatment for these patients in the absence of H2H trial comparing these two guideline recommended regimens.