Daratumumab Maintenance More Than Doubles Median PFS in Long-Term CASSIOPEIA Analysis

Daratumumab (Darzalex; Johnson & Johnson) maintenance more than doubled median progression-free survival (PFS) compared with observation among transplant-eligible patients with newly diagnosed multiple myeloma, according to long-term findings from the CASSIOPEIA trial (NCT02541383). Median PFS from the second randomization was about 91.7 months with daratumumab maintenance versus 44.6 months with observation, representing a 48% reduction in the risk of disease progression or death (HR, 0.52; 95% CI, 0.44-0.62; P < .0001).¹

The registry analysis, which was presented at the 23rd International Myeloma Society Annual Meeting, also found that daratumumab maintenance prolonged time to second disease progression or death (PFS2; HR, 0.72; 95% CI, 0.57-0.91; P = .0062).¹

CASSIOPEIA Examines Daratumumab Across Treatment Phases

CASSIOPEIA is a 2-part, open-label, randomized phase 3 trial evaluating daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma. During the first randomization, patients received induction and posttransplant consolidation with daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTd) or VTd alone. Patients who remained eligible underwent a second randomization to intravenous daratumumab maintenance every 8 weeks for up to 2 years or observation.²

Daratumumab is a CD38-directed cytolytic antibody. Its FDA-approved indications include use with VTd in transplant-eligible patients with newly diagnosed multiple myeloma, although single-agent daratumumab maintenance following transplantation is not a labeled indication.³

The new analysis used data from the IFM2023-03/MMY0010 follow-up registry, which enrolled 802 of 835 eligible patients who were alive at the completion of CASSIOPEIA. The 96% enrollment rate reduced the potential for substantial loss to long-term follow-up. Median follow-up reached approximately 102.9 months from the first randomization and 93.5 months from the second randomization.¹

Survival Benefits Persist Beyond 8 Years

From the first randomization, median PFS was about 87.8 months with D-VTd compared with 54.7 months with VTd, corresponding to an approximately 38% reduction in the risk of progression or death (HR, 0.62; 95% CI, 0.53-0.72; P < .0001). D-VTd also reduced the risk of death by 39% compared with VTd (HR, 0.61; 95% CI, 0.47-0.77; P < .0001).¹

At 96 months, estimated net survival was 94.3% with D-VTd and 80.7% with VTd. Net survival estimates disease-associated survival after accounting for expected mortality in the general population. The excess mortality rate was significantly higher among patients assigned to VTd than among those assigned to D-VTd (excess HR, 2.40; 95% CI, 1.47-3.91; P < .001).¹

The strongest PFS results were observed among patients who received D-VTd followed by daratumumab maintenance. Median PFS was not reached in this group, and 52.6% of patients remained alive without disease progression at 96 months.¹

Sustained MRD Negativity Supports Durable Control

Investigators evaluated minimal residual disease (MRD) in bone marrow after consolidation at sensitivity thresholds of 10^-5 and 10^-6. Five-year sustained MRD negativity at 10^-5, accompanied by a complete response or better, occurred in 23.1% of patients who received D-VTd followed by daratumumab maintenance. Rates were 17.9% with D-VTd followed by observation, 15.5% with VTd followed by daratumumab maintenance, and 5.6% with VTd followed by observation.¹

Within the VTd population, daratumumab maintenance significantly increased the likelihood of sustaining MRD negativity for 5 years compared with observation (OR, 3.23; P = .0007). Earlier CASSIOPEIA analyses also showed that incorporating daratumumab during induction, consolidation, and maintenance produced the deepest and most durable MRD responses.⁴

These findings strengthen the association between sustained MRD negativity and prolonged disease control. However, the maintenance comparison used observation rather than an active maintenance regimen, which limits direct application to current treatment decisions involving lenalidomide or multidrug maintenance.

Implications for Oncology Pharmacists

The long follow-up establishes that the benefits associated with daratumumab extended well beyond the planned treatment period. For oncology pharmacists, the findings underscore the importance of maintaining accurate treatment histories across induction, transplantation, consolidation, and maintenance because outcomes reflect the full treatment sequence.

Pharmacists also contribute to monitoring during daratumumab therapy, including evaluation for infusion-related reactions, cytopenia, and infections. Daratumumab can interfere with blood compatibility testing, making communication with transfusion services essential before treatment begins.³

After more than 8.5 years of follow-up, the CASSIOPEIA Registry supports daratumumab-based therapy as a strategy for achieving durable MRD negativity and long-term disease control in transplant-eligible newly diagnosed multiple myeloma.¹

REFERENCES

1. Corre J, Sonneveld P, Zweegman S, et al. Five-year sustained minimal residual disease negativity and survival with daratumumab maintenance in transplant-eligible newly diagnosed multiple myeloma: CASSIOPEIA Registry. Presented at: 23rd International Myeloma Society Annual Meeting; September 2026. Abstract OA-01.

2. Moreau P, Hulin C, Perrot A, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(10):1378-1390. doi:10.1016/S1470-2045(21)00428-9

3. Darzalex (daratumumab) injection, for intravenous use. Prescribing information. Janssen Biotech, Inc; revised 2025. Accessed September 24, 2026. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf

4. Corre J, Vincent L, Moreau P, et al. Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results. Blood. 2025;146(6):679-692. doi:10.1182/blood.2024027620