The FDA has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

The subcutaneous CD38 monoclonal antibody was previously approved with the same drug combination for patients with transplant-eligible disease. It also carries a previous indication for newly diagnosed transplant-ineligible multiple myeloma but with melphalan and prednisone, in addition to bortezomib.

The new approval marks the 12th indication for Darzalex Faspro and the fifth in newly diagnosed multiple myeloma, according to a company press release. It was based on the open-label CEPHEUS trial, which randomly assigned 395 patients equally to either daratumumab and hyaluronidase with VRd (D-VRd) or VRd alone for eight cycles, followed by lenalidomide and dexamethasone for all patients and continued daratumumab and hyaluronidase in the D-VRd group until progression.

At a median follow-up of 22 months, the minimal residual disease (MRD) negativity rate was 52.3% vs 34.8% in the D-VRd arm vs VRd alone. The progression-free survival hazard ratio was 0.60 (P = .0078).

Longer-term results published in Nature Medicine showed that over nearly 5 years, D-VRd led to higher rates of complete response or better (81.2% vs 61.6%; P < .0001) and sustained MRD negativity (48.7% vs 26.3%; P < .0001). Overall survival data were not yet mature.

Labelling warns of infections, neutropenia, thrombocytopenia, cardiac toxicity in patients with light chain amyloidosis, and other issues. The FDA announcement noted that the effectiveness of D-VRd has not been established in patients who refused stem cell transplants as their initial therapy.

The recommended Darzalex Faspro dose is 1800 mg of daratumumab and 30,000 units of hyaluronidase, administered subcutaneously.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com