Characterization of Newly Diagnosed Multiple Myeloma (NDMM) Patients with Early Progression Following Induction with Daratumumab, Lenalidomide, Bortezomib and Dexamethasone (D-RVd)

Introduction: The phase 3 PERSEUS trial has established daratumumab with lenalidomide, bortezomib and dexamethasone (D-RVd) as standard of care induction therapy in newly diagnosed myeloma (NDMM) showing impressive depth of response and progression free survival (PFS). We have previously published our institutional experience with 326 patients induced with D-RVd followed by stem cell transplant and risk-stratified maintenance therapy showing a post-transplant ORR of 99.3% and 2 year PFS 93% with median follow up of 19.1 months. Despite these impressive results, there is still a subset of patients who experience early relapse. Here, we identify and describe these patients with suboptimal benefit to D-RVd induction.

Methods: We identified 326 NDMM patients treated with D-RVd induction therapy from April 2018 to August 2022. Demographics, clinical characteristics and outcomes were obtained from our institutional review board-approved myeloma database. Responses and progression were evaluated per International Myeloma Working Group (IMWG) Uniform Response Criteria. High risk (HR) disease is defined by presence of del(17p), t (4;14) and t(14;16). Data cutoff was June 30, 2024.

Results: The median follow up is 33.2 months. Of the 326 patients, 44 patients had documented disease progression by data cutoff. Notable patient characteristics of this cohort compared to the larger D-RVd cohort include median age of diagnosis 59 v 61, 64% v 54.6% male, 48% vs 41.7% black, RISS 3 30% v 6.1% and HR 27% v 15.4%, respectively. Post-induction, comparative overall response rates (ORR) between patients with early relapse and the overall cohort was 97.8 v 99.6% with a ≥VGPR of 70.4 v 86.5%, respectively. Post-transplant, the ≥VGPR of 84.2% v 95.6%. Median time to progression was 22.7 months. Most common first-line therapies after relapse included daratumumab, carfilzomib, dexamethasone (DKd) (n=14, 32%), daratumumab, pomalidomide, dexamethasone (DPd) (n=8, 18%), and carfilzomib, pomalidomide, dexamethasone (KPd) (n=5, 11%). The median OS has not been reached. Estimated 3 year survival is 82%. PFS2, MRD status, risk based on updated IMS definitions and multivariate analysis with updated follow up will be presented at the meeting.

Discussion:

D-RVd is a highly effective induction regimen that can lead to impressive long-term outcomes, however, there remains a patient population that does not experience this same benefit. This is the largest real world dataset of patients treated with D-RVd induction with data on patients with early progression. Patient with early progression were more likely to be male, have R-ISS 3 and HR disease, and though a majority of patients achieved VGPR, it was comparatively less than the overall cohort. Further study is needed to better understand and identify this cohort of patients early so that there can be consideration of alternative treatment approaches to optimize outcomes.