Associate Professor Winship Cancer Institute, Emory University Atlanta, Georgia, United States
Introduction: Quadruplet induction with DRVd demonstrated reduced risk of progression or death compared to RVd among newly diagnosed multiple myeloma (NDMM) patients 18-70 years old in the phase 3 PERSEUS trial (Sonneveld et al, NEJM 2023). However, the impact in patients ≥ 65 years (25.5% of patients) was less pronounced with HR for progression free survival (PFS) of 0.97 (CI 95%, 0.52-1.81) versus HR 0.30 (95% CI, 0.20-0.46) in patient < 65 years. We have previously presented institutional data of 326 patients induced with DRVd compared to 1000 historic controls induced with RVd showing comparable PFS to PERSEUS trial (Joseph et al, ASH 2023). Here, we present a comparative analysis specifically in transplant-eligible patients < 65 years versus patients ≥65 years of age to address the benefit of DRVd among older NDMM patients.
Methods: 1000 consecutive NDMM patients treated with RVd between January 2007- August 2016, and 326 NDMM patients treated with DRVd induction therapy from April 2018 - August 2022 were included in this analysis. Patient were treated with 4-6 cycles of induction therapy, followed by autologous stem cell transplant (ASCT) and risk-adapted maintenance therapy until disease progression. Demographic and outcomes data were obtained from our institutional review board-approved myeloma database and with manual abstraction. Responses and progression were evaluated per IMWG Response Criteria.
Results: Though these are sequential cohorts, the arms are well balanced with similar median age (DRVd vs RVd: 62.1 vs 61.2 years, respectively). 55.5% and 54.6% are male; 41.7% vs 36.3% are black; and the most common Isotype is IgG in 65.2% and 61.6% of patients in the DRVd and RVd cohorts, respectively. In the RVd cohort, 314 (31.4%) patients are ≥ 65 years, and in DRVd, 106 patients (32.5%) are ≥ 65 years, p=0.385. For the patients ≥ 65 years specifically, high risk disease was present in 13.7% and 16.2% (p=0.572), ISS stage 3 in 21.0% vs 21.3% (p=0.304) and R-ISS stage 3 in 5.1% and 8.7% (p=0.588) of patients in the DRVd and RVd cohorts, respectively. ≥VGPR rates 88.7% versus 66.4% in DRVd and RVd ≥65 years cohorts.
The 4-year PFS for patients ≥65 in DRVd vs RVd cohorts was 95% vs 59%, and the 4-year PFS for patients < 65 in the DRVd vs RVd cohorts was 82% vs 61%.
Conclusions: DRVd is a highly effective induction regimen demonstrating efficacy in the phase 3 setting, and that we have shown improves upon outcomes in a historical NDMM population treated with RVd in terms of depth of response and PFS benefit. Though benefit was not seen for patients 65-70 years of age in the phase 3 study, our data reflecting real-world clinical practice suggests that these patients can and do benefit from the addition of daratumumab upfront.
