Associate Professor Winship Cancer Institute, Emory University Atlanta, Georgia, United States
Introduction: DRVd has been established as standard of care induction therapy following the randomized phase 3 PERSEUS study (Sonneveld et al, NEJM 2023). We previously presented data from our institutional dataset of 326 patients induced with DRVd demonstrating comparable depth of response and progression free survival (PFS) to the clinical trial experience (Joseph et al, ASH 2023). In aggregate, D-RVd induction yielded impressive very good partial response (VGPR) rates and these patients experienced prolonged PFS. The question of whether those that achieved < VGPR with DRVd experience similar outcomes is unknown.
Methods: 1000 consecutive NDMM patients treated with RVd between 1/2007- 8/2016, and 326 NDMM patients treated with DRVd induction therapy from 4/2018 - 8/2022 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. We evaluated the outcomes of patients achieving < VGPR compared to ≥VGPR post-induction and post-transplant in the RVd and DRVd cohorts. The primary outcome of interest is PFS. Demographic, clinical and outcomes data were obtained from our IRB-approved myeloma database. Responses were evaluated per IMWG Uniform Response Criteria.
Results: The two cohorts are balanced: median age 62.1 vs 61.2 years, male 55.5% and 54.6%; black 41.7% vs 36.3%; most common isotype is IgG in 65.2% and 61.6% of patients in the D-RVd and RVd cohorts, respectively. High risk disease in 15.4 and 17.8%, ISS stage 3 in 20.2% vs 23.4% and R-ISS stage 3 in 6.1% and 11.5% of patients in the DRVd and RVd cohorts. Post-induction, the overall response rate (ORR) in the D-RVd cohort was 99.6% with 86.5%achieving ≥VGPR and 44 patients (13.5%) achieved < VGPR. This contrasts with the RVd group where 317 evaluable patients (32.4%) failed to achieve a VGPR. Post-transplant, of the 271 response evaluable patients, 95.6% achieved ≥VGPR and 4.4% achieved < VGPR. In the RVd group,129 (13.2%) failed to achieve a VGPR post-transplant.
As shown in figure 1, the PFS among patients who achieved ≥VGPR both post-induction (panel A, p< 0.001)) and post-transplant (panel C, p< 0.001) with D-RVd induction experienced significantly improved PFS compared to the RVd cohort. However, patients who failed to achieve VGPR post-induction (panel B, p=0.994) and post-transplant (panel D, p=0.624) experienced similar PFS to the RVd cohort, suggesting a biologically aggressive group of patients prone for early relapse and inferior PFS.
Conclusions: DRVd is a highly effective induction regimen with superior efficacy in terms of improved ≥VGPR rates and PFS compared to RVd. Using a quadruplet regimen, very few patients achieve < VGPR post-induction (13.5%) and/or post-transplant (4.4%). However, the outcomes of patients who fail to achieve a VGPR is no better than the RVD cohort, suggesting the need for a response-adapted approach to deepen response and improve long term outcomes.
