U.S. FDA Expands Darzalex Faspro with VRd Approval for Newly Diagnosed Multiple Myeloma Patients Ineligible for Transplant

On January 27, 2026, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc) with VRd, a combination of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd), for newly diagnosed multiple myeloma patients who cannot receive a stem cell transplant.

Some people who are newly diagnosed with multiple myeloma cannot receive an autologous stem cell transplant due to other health concerns. For these patients, the current standard of care treatment is the triplet therapy VRd. Recent clinical trials have found that adding daratumumab and hyaluronidase (Darzalex Faspro) improves outcomes for these patients compared to VRd alone.

“This approval marks the twelfth indication for Darzalex Faspro overall and fifth in newly diagnosed multiple myeloma, underscoring its role as foundational therapy for both newly diagnosed and relapsed/refractory patients,” said June Lanoue, U.S. President, Hematology of Johnson & Johnson Medicine in a press release from Johnson & Johnson. “CEPHEUS demonstrated the efficacy of a Darzalex Faspro-based quadruplet as frontline standard of care. With this approval, patients can receive D-VRd when they are first diagnosed with multiple myeloma, an important milestone as we work to one day deliver a functional cure. 

How does daratumumab and hyaluronidase with VRd treat myeloma?

Daratumumab is a monoclonal antibody. It binds to the CD38 protein on the surface of myeloma cells to stop them from growing. Daratumumab with hyaluronidase is an injection that is given under the skin in the stomach area. It takes about 3 to 5 minutes to give the injection. 

The VRd “triplet” therapy combines bortezomib, lenalidomide, and dexamethasone. 

• Bortezomib (Velcade) is a proteasome inhibitor.

• Lenalidomide (Revlimid) is an oral immunomodulatory drug.

• Dexamethasone is a steroid. 

These drugs work together to kill myeloma cells, activate the immune system, and stop new myeloma cells from growing. 

The study that led to expanding the indication for daratumumab and hyaluronidase

This approval was based on results from the CEPHEUS clinical trial (NCT03652064). This study compared the D-VRd quadruplet therapy with VRd triplet therapy alone. There were 395 patients who were randomly assigned to receive either D-VRd or VRd. 

• The minimal residual disease (MRD) negativity rate was 52.3% in the D-VRd group and 34.8% in the VRd group.

• People treated with D-VRd were 40% less likely to have their cancer progress than patients treated with VRd. 

What are the common side effects of D-VRd?

The most common side effects (20% or more) of this quadruplet therapy include:

• Upper respiratory tract infection

• Sensory neuropathy

• Musculoskeletal (muscle and bone) pain

• Diarrhea

• Fatigue

• Edema (swelling)

• Rash

• Motor dysfunction

• COVID-19

• Constipation

• Sleep problems

• Cough

• Pneumonia

• Kidney problems

• Dizziness

• Nausea

• Urinary tract infection

• Fever

• Abdominal pain

• Shortness of breath

• Appetite loss

• Bruising

Next steps for people living with newly diagnosed multiple myeloma

If you or a loved one was recently diagnosed with multiple myeloma and cannot receive a stem cell transplant, ask your healthcare team about your treatment options and if DVR-d or ongoing clinical trials may be right for you. 

Questions to ask your care team about D-VRd

Consider asking your care team the following questions about D-VRd: 

• Am I eligible for an autologous stem cell transplant? If not, is D-VRd a treatment option for me?

• What side effects should I expect with this therapy?

• What will my dosing schedule be?

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SOURCES: 

• DARZALEX FASPRO®-based quadruplet regimen approved in the U.S. for newly diagnosed patients with multiple myeloma who are transplant ineligible

• FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma

• A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy