The FDA approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen) in combination with pomalidomide and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor.

Efficacy was evaluated in the open-label, active-controlled, phase 3 APOLLO trial (ClinicalTrials.gov Identifier: NCT03180736). Findings from the study were presented at the 2020 annual meeting of the American Society of Hematology (abstract 412) and recently published in Lancet Oncology (2021;22[6]:801-812). 

In the trial, investigators randomly assigned 304 patients in a 1:1 fashion to receive daratumumab (1,800 mg per day) and hyaluronidase (30,000 units per day) with pomalidomide (4 mg per day) and dexamethasone (40 mg, or 20 mg per week for patients >75 years of age) (Pd) or Pd alone. Daratumumab and hyaluronidase were administered subcutaneously once weekly from weeks 1 to 8, once every two weeks from weeks 9 to 24 and once every four weeks starting at week 25, until disease progression or unacceptable toxicity. Pomalidomide was administered once daily orally on days 1 to 21 of each 28-day cycle. 

The study met its primary end point of improved progression-free survival (PFS), demonstrating that daratumumab and hyaluronidase combined with Pd significantly reduced the risk for progression or death by 37% over that seen with Pd alone (hazard ratio [HR], 0.63; 95% CI, 0.47-0.85; P=0.0018). Median PFS was 12.4 months in the group receiving daratumumab and hyaluronidase along with Pd versus 6.9 months in the group receiving Pd alone.

The overall response rate was significantly higher with daratumumab and hyaluronidase combined with Pd compared with Pd alone (69% vs. 46%), as were the rates of complete response or better (25% vs. 4%) and very good partial response or better (51% vs. 20%). In addition, more patients treated with daratumumab and hyaluronidase combined with Pd showed a negative status for minimal residual disease than patients receiving Pd alone (9% vs. 2%). 

The most common adverse events (≥20%) observed in patients with multiple myeloma treated with daratumumab and hyaluronidase combined with Pd were fatigue, pneumonia, upper respiratory tract infection and diarrhea.
Permanent treatment discontinuation due to an adverse event occurred in 2% of patients who received daratumumab and hyaluronidase combined with Pd. 

For more information, see the complete prescribing information for daratumumab and hyaluronidase.

—Clinical Oncology News Staff

Based on press releases from the FDA and Janssen.