U.S. FDA Approves Daratumumab Combination for High-Risk Smoldering Multiple Myeloma

On November 6, the U.S. Food and Drug Administration (FDA) approved the combination daratumumab and hyaluronidase, sold as Darzalex Faspro (Johnson & Johnson), for adults with high-risk smoldering multiple myeloma. The drug combines the targeted therapy daratumumab with hyaluronidase, which helps it absorb into the body.

Smoldering myeloma is a slow-growing precursor stage to multiple myeloma. A person with smoldering myeloma has signs of myeloma, such as abnormal plasma cells and/or protein in the blood and urine, but few or no symptoms. About 5 out of 10 people with high-risk smoldering myeloma will go on to develop multiple myeloma within two years of their diagnosis, but there are few treatment options. Outside of clinical trials, smoldering myeloma is monitored until it progresses to myeloma. 

Daratumumab with hyaluronidase is the first drug specifically approved to treat high-risk smoldering myeloma. The approval was based on the phase 3 AQUILA study. The study compared active monitoring, also called “watch and wait,” to treatment with the daratumumab combination. Treatment with daratumumab reduced the risk of disease progression by 51% compared to active monitoring. After a median follow-up of almost 5.5 years, 63.1% of people treated with daratumumab had not progressed to active myeloma. In comparison, 40.7% of people in the “watch and wait” group had not progressed to active myeloma. 

“Until now, patients diagnosed with smoldering multiple myeloma only have the option to watch and wait for any active signs of progression to active disease,” said Peter Voorhees, M.D. of the Atrium Health/Levine Cancer Institute in Charlotte, NC. “Results from AQUILA demonstrated Darzalex Faspro significantly delayed disease progression, underscoring the role of early disease intervention for patients with high-risk smoldering multiple myeloma.”

How does daratumumab (Darzalex Faspro) treat smoldering myeloma?

Darzalex Faspro is a combination of daratumumab and hyaluronidase. Daratumumab is a type of targeted therapy. It targets the CD38 protein, which is found on plasma cells. When daratumumab binds to the CD38 protein, it kills myeloma cells. It also activates the immune system against the damaged myeloma cells. Hyaluronidase makes it easier for daratumumab to be absorbed into subcutaneous tissue. This is so daratumumab can be given as an injection instead of an IV infusion.

Daratumumab with hyaluronidase is given as an injection in the abdomen (belly). Patients receive the injection on a regular dosing schedule.

What are the side effects of daratumumab (Darzalex Faspro)?

The most common side effects of daratumumab for people with high-risk smoldering myeloma were: 

• Upper respiratory tract infection

• Musculoskeletal (muscle and bone) pain

• Fatigue

• Diarrhea

• Rash

• Sleep problems

• Neuropathy (nerve problems)

• Reactions at the injection site

During the clinical trial, fewer than 6% of patients stopped treatment due to side effects. 

Never miss a multiple myeloma update! The HealthTree newsletter delivers myeloma research updates, FDA approvals, and more directly to your inbox. 

Sign Up Today

Sources: 

• DARZALEX FASPRO^® is the first and only treatment approved by the U.S. FDA for patients with high-risk smoldering multiple myeloma
• Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma