Sub-Q Daratumumab/VRd Wins Approval in Newly Diagnosed Multiple Myeloma

The FDA has approved subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd; Darzalex Faspro-VRd) for the treatment of patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT).¹

The combination’s approval in this patient population is supported by data from the open-label, randomized, active-controlled CEPHEUS trial (NCT036520640). Efficacy was evaluated via minimal residual disease (MRD) negativity and progression-free survival as determined by independent review committee.

The MRD negativity rate in the experimental arm was 52.3% vs 34.8% in the VRd arm (P = .0005). Further, the combination reduced the risk of death or disease progression by 40% (PFS HR, 0.60; 95% CI, 0.41-0.88; P = .0078). The recommended dosage of daratumumab is 1800 mg of daratumumab and 30,000 units of hyaluronidase.

“It’s given as 1 infusion, together with daratumumab and hyaluronidase,” explained Stephanie Mompoint, APRN, a research advanced practice nurse at the University of Miami in Florida, in an interview with Oncology Nursing News. “You’re going to have that reaction from the patient seeing the needle when they see the volume that’s going to be inserted. It’s [essential to] reassure them and let them know that the premedications will help with reaction, and, as the nurse, to be alert for possible immediate systemic reactions.”

Safety and Administration With Subcutaneous Daratumumab

“Just because the drug is given subcutaneously, that doesn’t mean that the systemic reactions are not going to happen, like fevers [and] chills,” said Mompoint. “If your patient starts to have chills, even while you’re doing the subcutaneous injection, you have to stop the injection and give the patient time to settle down, take their temperature, do their vitals, and call the provider if extra medication is needed.”

The prescribing information for subcutaneous daratumumab includes warnings for administration reactions including hypersensitivity, infections, cytopenias, embryo-fetal toxicity, interference with cross-matching and red blood cell antibody screening, and cardiac toxicity for patients with light chain amyloidosis.

Heather Wenberg, BSN, RN, OCN, a regional director of nursing at the American Oncology Network, added in an interview with Oncology Nursing News that subcutaneous daratumumab requires less premedication than its intravenous formulation.

“If patients were getting the IV version [of daratumumab], they would have an IV in their arm, [receiving] premeds all the time, and they would have a 3-hour infusion each time,” said Wenberg. “[With] the subcutaneous option…patients can be in and out of the clinic within 2 hours at the most.”

Subcutaneous Daratumumab in Multiple Myeloma

The combination of subcutaneous daratumumab with VRd was approved in July 2024 for induction and consolidation in patients with newly diagnosed multiple myeloma who are eligible for ASCT.² Most recently, subcutaneous daratumumab became the first therapy approved by the FDA for patients with smoldering multiple myeloma.³

The agent has multiple other approved indications in multiple myeloma including in combination with carfilzomib (Kyprolis) and dexamethasone for those with relapsed or refractory disease who have received 1 to 3 prior lines of therapy and in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for patients who have received at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor.

Further approvals of subcutaneous daratumumab in multiple myeloma include the inclusion of the subcutaneous therapy in indications already approved for its intravenous formulation.

Looking for more information on administering subcutaneous daratumumab in patients with multiple myeloma? Check out our Rx Road Map: Subcutaneous Daratumumab in Multiple Myeloma series for insights from experts.

References

1. FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. FDA. January 27, 2026. Accessed January 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-newly
2. FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for multiple myeloma. FDA. July 30, 2024. Accessed January 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-multiple
3. FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma. FDA. November 6, 2025. Accessed January 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-high-risk-smoldering-multiple-myeloma