Daratumumab Plus VRd Outperforms VRd Alone for Multiple Myeloma

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Newly diagnosed patients with multiple myeloma who received daratumumab along with the standard care regimen of bortezomib, lenalidomide, and dexamethasone (VRd) had significantly higher rates of survival without disease progression compared with those who received VRd alone. Results from the phase III Perseus trial were reported at the 2023 ASH Annual Meeting & Exposition (Abstract LBA-1). 

At a median follow up of 47.5 months, the estimated rate of progression-free survival, the trial’s primary endpoint, was significantly improved with D-VRd vs VRd. Patients who received daratumumab plus VRd (D-VRd) had an estimated 4-year progression-free survival rate of 84.3% compared with 67.7% among those receiving VRd alone, a difference of about 17%. 

“We were not surprised to see the difference with the addition of daratumumab, but we were very surprised by the magnitude of the difference between the two arms,” said Pieter Sonneveld, MD, PhD, Professor of Hematology at Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and the study’s lead author. “This difference is of major clinical significance to the patient in terms of their well-being and [remaining] disease-free.” 

Daratumumab is a monoclonal antibody targeting a protein that is overexpressed in multiple myeloma cells; it has previously been approved for use in patients who are ineligible for stem cell transplant or for cancers that relapse or do not respond to standard initial therapies. The new phase III Perseus trial is the first to test its use as part of front-line therapy for newly diagnosed multiple myeloma in a head-to-head comparison with the current standard of care. 

With these results, [I expect] this treatment schedule will be the future standard for these patients.
— Pieter Sonneveld, MD, PhD

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Perseus Details

For the trial, researchers enrolled 709 patients newly diagnosed with multiple myeloma across multiple European countries who were considered eligible for autologous stem cell transplantation, which is part of the standard treatment for multiple myeloma. Patients received up to six cycles of VRd induction therapy in 28-day cycles; proceeded to a stem cell transplant if possible; and continued taking lenalidomide afterward as maintenance therapy. Patients who were randomly assigned to receive D-VRd also received daratumumab via subcutaneous injections during both the induction and maintenance phases of the trial. Researchers noted that elements of the trial design—including the use of subcutaneous injections rather than daratumumab infusions and the administration of treatment in 28-day cycles rather than 21-day cycles—were intended to make the regimen gentler on patients and reduce the likelihood of adverse effects. 


At the time of data cutoff, 613 participants had completed the induction/consolidation phase of treatment and patients had been followed for a median of just under 4 years. Progression-free survival was significantly higher in the D-VRd arm, and subgroup analyses showed that this was consistent across all patient groups, including those with more advanced and higher-risk forms of multiple myeloma. 

Of patients who received the D-VRd regimen, 87.9% saw a complete response or better, compared with 70.1% among those who received standard care. Patients in the D-VRd arm also had a significantly higher rate of measurable residual disease (MRD) negativity, which was achieved in 75.2% of patients receiving D-VRd and 47.5% of those receiving VRd alone. The amount of follow-up time is not yet sufficient to compare trends in overall survival rates. 

The rate of serious treatment-related adverse events was higher in the D-VRd arm, with 57% of patients who received daratumumab experiencing such events compared with 49.3% among those receiving VRd alone. However, researchers noted that adverse events led to treatment discontinuation significantly less often in the D-VRd arm, and most adverse events were short-term and temporary. The most common grade ≥ 3 adverse events were low white blood cell counts, low platelet counts, diarrhea, pneumonia, and fever.

Taken together, Dr. Sonneveld said that the results suggest that D-VRd outperforms VRd alone for frontline multiple myeloma treatment with a manageable safety profile. “With these results, [I expect] this treatment schedule will be the future standard for these patients,” he said. 

A follow-on analysis will examine the longer-term outcomes of stopping daratumumab after 2 years of maintenance therapy in patients who achieve MRD negativity. 

Disclosure: The study was funded by the European Myeloma Network with support from Janssen Pharmaceuticals. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.