In patients with myeloma who are able to have a transplant of their own stem cells, the standard treatment was the three-drug combination VRd. This study showed that adding a fourth drug, daratumumab (an injection under the skin), makes the response much deeper: three quarters of patients reached a state in which myeloma cells could not be found even with very sensitive tests, and after 4 years more than 84% of patients had no progression of their disease. Drops in white blood cells and platelets were somewhat more common.
Key results
84.3% vs 67.7%
48-month progression-free survival
HR 0.42 (95% CI: 0.30 to 0.59); P<0.001; median follow-up 47.5 months
Transplant-eligible newly diagnosed multiple myeloma (age 70 years or younger)Cycle length: Every 28 daysOn the page “Blood cancers (leukaemia, lymphoma and myeloma)” · Treatment regimens and dosing in multiple myeloma
Transplant-eligible newly diagnosed multiple myeloma (age 70 years or younger)
On daratumumab days, dexamethasone is given as premedication. Daratumumab + lenalidomide maintenance in PERSEUS was investigational, and its effect is not regarded as established in the label.
D-VRd followed by autologous transplantation and D-R maintenance (PERSEUS trial)
Newly diagnosed myeloma in patients eligible for autologous transplantation (up to 70 years of age in PERSEUS)Each drug’s schedule in the tableOn the page “Multiple myeloma” · Newly diagnosed myeloma: transplant-eligible patients
Newly diagnosed myeloma in patients eligible for autologous transplantation (up to 70 years of age in PERSEUS)
Drug
Dose
Route
Schedule
Induction (Cycles 1–4) and consolidation (Cycles 5 and 6)
10 mg once daily (after 3 cycles, 15 mg if tolerated)
Oral
Days 1–28 (continuous)
Cycle schedule
Induction and consolidation: bortezomib, lenalidomide and dexamethasone in 28-day cycles, daratumumab weekly then every 2 weeks; maintenance: daratumumab every 4 weeks and lenalidomide continuously
Duration
4 cycles of induction, transplantation, 2 cycles of consolidation (within 12 weeks after transplantation and after engraftment), then maintenance until progression; daratumumab is stopped after at least 24 months of maintenance and 12 months of sustained MRD negativity
Doses from the ClinicalTrials.gov record NCT03710603 and the FDA label for DARZALEX FASPRO; results from PERSEUS. According to the FDA label, the efficacy of daratumumab in the maintenance phase has not been separately established, although the EHA-EMN guideline regards the combination of daratumumab and lenalidomide as the new standard for maintenance.
Newly diagnosed transplant-eligible myeloma: induction and consolidationEach drug’s schedule in the tableOn the page “VRd and D-VRd regimens in myeloma”
Newly diagnosed transplant-eligible myeloma: induction and consolidation
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Treatment arms and regimens
1D-VRd (daratumumab + VRd)
Four induction cycles and two consolidation cycles of 28 days (before and after high-dose chemotherapy and autologous transplantation):
Daratumumab 1800 mg subcutaneously weekly in cycles 1 and 2, then every 2 weeks in cycles 3 to 6;
bortezomib 1.3 mg/m² subcutaneously on days 1, 4, 8 and 11 (cycles 1 to 6);
Maintenance: daratumumab every 4 weeks with lenalidomide 10 mg daily (may be increased to 15 mg); daratumumab was stopped in patients with sustained MRD negativity for 12 months and after at least 24 months of maintenance.
2VRd
The same induction and consolidation regimen without daratumumab (bortezomib, lenalidomide and dexamethasone at the doses above) and autologous transplantation, then maintenance with lenalidomide 10 mg daily until disease progression.
Source of the regimen details: ClinicalTrials.gov NCT03710603
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with newly diagnosed multiple myeloma who were candidates for autologous stem cell transplantation.
Endpoints
Primary endpoint: progression-free survival.
Key secondary endpoints: complete response or better and minimal residual disease (MRD) negativity.
Safety and side effects
Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd vs 51.0% with VRd) and thrombocytopenia (29.1% vs 17.3%). Serious adverse events 57.0% vs 49.3%.
Clinical significance and place in guidelines
Based on this study, D-VRd was approved by the FDA and EMA in 2024 for induction and consolidation in transplant-eligible patients. A four-drug regimen containing an anti-CD38 antibody (D-VRd or Isa-VRd) is now the standard first-line treatment for transplant-eligible patients in the EHA-EMN and IMWG guidelines.
Limitations
The study was open-label. Overall survival data were immature at the time of this report. The D-VRd group also received daratumumab during maintenance, so the separate contributions of induction and maintenance cannot be distinguished. The role of transplantation in the era of four-drug regimens was not assessed in this study.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
Who are you reading this site as?
Your choice applies to every page; change it any time from the bottom of the page.