At the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, researchers from Emory University presented a real-world comparison of the largest cohort of patients with newly diagnosed multiple myeloma consecutively treated with either bortezomib, lenalidomide, and dexamethasone (VRd) or VRd plus daratumumab (D-VRd) in terms of response and long-term outcomes.1 Their findings essentially mirrored those of the phase III PERSEUS trial, reported as a late-breaking abstract by Sonneveld et al, showing a robust benefit with the addition of the anti-CD38 antibody.
Definite Improvement With D-VRd
“D-VRd is a highly effective induction regimen that can improve upon outcomes in a historical population…treated with VRd in terms of depth of response and progression-free survival benefit…. This analysis provides an early glimpse of the promising progression-free survival and overall survival benefit, not only in standard-risk patients, but also in patients with high-risk cytogenetic and disease features,” the researchers concluded.
Nisha Joseph, MD, Assistant Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, reported outcomes for 326 patients with newly diagnosed disease treated with D-VRd induction between 2018 and 2022,1 compared with those of 1,000 consecutive patients treated with VRd from 2007 to 2016.2 Daratumumab was dosed intravenously or subcutaneously weekly throughout induction, with 21-day treatment cycles. Of note, in contrast to the GRIFFIN trial, consolidation was not given in either cohort, and maintenance therapy consisted of lenalidomide alone until disease progression for standard-risk patients and a triplet induction regimen for 3 years for high-risk patients. Approximately 99% of both cohorts underwent transplantation.
“The best way to visualize depth of response is to look at the [very good partial response] rate or better, and you see definite improvement with D-VRd,” Dr. Joseph said. “Postinduction, that rate improved from 67.5% with VRd to 86.4% with D-VRd, and posttransplant, it improved from 86.8% to an impressive 95.6%. So does this improved depth of response translate into a survival benefit?”
Further Considerations
Though the median follow-up for the D-VRd cohort is significantly shorter (18 months vs 87 months for VRd), quadruplet induction appeared to yield a progression-free survival benefit in both standard-risk and high-risk patients. For all patients receiving VRd, the median progression-free survival was 67.5 months (hazard ratio [HR] = 0.34; P < .001), and median overall survival was 128.9 months (HR = 0.54; P = .037), or almost 6 and 11 years, respectively. Neither endpoint has been reached with D-VRd, either in the overall population or for either risk category.
At 2 years, the progression-free survival rates were 93% with VRd and 98% with D-VRd, and the overall survival rates were 91% and 94%, respectively. Strikingly, at 4 years, the progression-free estimate was 61% vs 85%, respectively (P < .001), she said.
Multivariate analysis showed that patients with stage III disease incurred a triple risk for disease progression and an almost quadruple risk for death without daratumumab (P < .001). However, D-VRd induction was associated with a 66% reduction in the risk of disease progression or death (P < .001); maintenance therapy of either type conveyed a 40% reduction in disease progression (P < .001) and a 60% reduction in death (P < .001). In high-risk patients, the 2-year progression-free survival rate with VRd vs D-VRd was 69% vs 83%, with 79% vs 94% alive at that time.
“We are seeing a very similar 4-year estimated progression-free survival as in the randomized trials setting. This begs the question of who benefits from multiagent maintenance, and what is the optimal duration of this maintenance,” Dr. Joseph commented. The assessment of measurable residual disease is underway
DISCLOSURE: Dr. Joseph has served as a consultant to Janssen Oncology and has received honoraria from BMS.
REFERENCES
1. Joseph NS, Dicamillo SM, Roberst D, et al: Comparison of response and survival outcomes in newly diagnosed transplant-eligible multiple myeloma patients treated with RVd vs daratumumab and RVd. 2023 ASH Annual Meeting & Exposition. Abstract 647. Presented December 10, 2023.
2. Joseph NS, Kaufman JL, Dhodapkar MV, et al: Long-term follow-up results of lenalidomide, bortezomib, and dexamethasone induction therapy and risk-adapted maintenance approach in newly diagnosed multiple myeloma. J Clin Oncol 38:1928-1937, 2020.
