The DVRd Regimen

This standard-of-care quadruplet combination is now FDA-approved for the majority of patients with newly diagnosed multiple myeloma 

On January 27, 2026, the U.S. Food and Drug Administration (FDA) approved the use of the quadruplet (4-drug) combination of Darzalex Faspro® (daratumumab + hyaluronidase-fihj) + Velcade® (bortezomib) + Revlimid® (lenalidomide) + dexamethasone [DVRd] for adult patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for an autologous stem cell transplant (ASCT). DVRd, a highly effective and well-tolerated combination therapy for patients with myeloma, was previously approved by the FDA in 2024 for patients who are eligible for ASCT.

The drugs in the DVRd regimen

Although it may seem that being treated with 4 drugs is a lot of therapy, each medication in the DVRd regimen is from a different drug class, each with its own way of attacking myeloma while enhancing the activity of the other drugs:

• Darzalex Faspro, a newer formulation of Darzalex® (daratumumab), is a monoclonal antibody that targets and binds to the CD38 protein on the surface of myeloma cells and enlists the cells of the immune system to help attack and kill myeloma cells. Darzalex Faspro is given as a subcutaneous (SQ) injection under the skin of the abdomen at a doctor’s office in 3 to 5 minutes, while it also reduces the rate of an infusion-related reaction (IRR) to 13% vs. 34% with the original Darzalex intravenous (IV) formulation.
• Velcade is a proteasome inhibitor that interferes with the normal function of a joined group (“complex”) of enzymes (“proteases”), causing damaged and unwanted proteins to build up in the myeloma cell, causing myeloma cells to die.
• Revlimid is an immunomodulatory agent that can modify, enhance, or suppress the functioning of the immune system. It helps the cells of the immune system to recognize and destroy myeloma cells.
• Dexamethasone is a steroid that can kill myeloma cells directly, increase the efficacy of other drugs used to treat myeloma, inhibit the survival of myeloma cells, and block the release of cytokines that promote myeloma cell growth.

It is because these four drugs work so well together that DVRd can lead to such good outcomes for many patients.

CEPHEUS clinical trial of DVRd

The FDA expanded approval of DVRd in 2026 was based on data from the CEPHEUS clinical trial in patients with NDMM who were ineligible for ASCT or who declined ASCT as frontline therapy, the initial treatment used in an effort to achieve response in a newly diagnosed patient. Of the 395 study patients, 197 were randomized to the DVRd arm and 198 to the VRd arm without Darzalex Faspro.

MRD and PFS efficacy measures

The CEPHEUS clinical trial demonstrated significant efficacy as measured by overall minimal residual disease (MRD)-negativity and progression-free survival (PFS). 

MRD is the presence of residual cancer cells after treatment has been completed and complete response (CR) has been attained. MRD-negativity means that not even 1 myeloma cell was found in 100,000 or 1,000,000 sampled bone marrow plasma cells (depending on the test being used). In the DVRd arm of the CEPHEUS study, the rate of MRD-negativity was 52.3% vs. 34.8% in the VRd arm, a significant difference.

PFS is the length of time during and after treatment that a patient lives with myeloma but the disease does not relapse. At 54 months, approximately 68% of study patients in the DVRd arm remained progression-free vs. approximately 48% in the VRd arm. DVRd demonstrated a 43% lower risk of progression or death when compared to the VRd arm of the study. Median PFS, the midpoint in a set of data, was not reached for patients in the DVRd arm, indicating superior, long-lasting, durable responses compared to patients in the VRd arm of the study.

What DVRd means for patients

The CEPHEUS study demonstrate that DVRd is a new standard of care, a benchmark treatment that is widely accepted by medical experts as the most appropriate for patients with NDMM who are not proceeding to transplant as frontline therapy.

Similarly, the PERSEUS clinical trial, which was the basis of the 2024 FDA approval of DVRd in transplant-eligible patients with NDMM, showed significantly improved PFS and increased depth of response (DpR), demonstrating that DVRd is a new standard of care for ASCT-eligible patients with NDMM.

“DVRd has increasingly become the standard-of-care regimen for the majority of the transplant-eligible and fit or intermediate- fit transplant-ineligible newly diagnosed myeloma patients, following the paradigm of picking the best therapies to give all patients the opportunity to achieve best responses and survival outcomes,” says Dr. Saad Z. Usmani, principal investigator of the CEPHEUS clinical trial, myeloma specialist and cellular therapist at Memorial Sloan Kettering Cancer Center in New York City, as well as a member of the IMF Scientific Advisory Board and the IMF International Myeloma Working Group. 

STAY INFORMED! Contact the IMF InfoLine with your myeloma-related questions and concerns. Phone lines are open 9 a.m. to 4 p.m. (Pacific) Monday through Friday at 1.818.487.7455 or you can email us at [email protected] or visit mmsm.link/infoline to schedule a convenient time to talk with an IMF InfoLine Coordinator.

(This article was originally published in the 2026 Spring Edition of the IMF's quarterly publication, Myeloma Today. Read the full publication here.)