FDA Approval Insights: Subcutaneous Daratumumab in Multiple Myeloma

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Jessica Hergert.

OncLive^® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Maria-Victoria Mateos, MD, PhD, associate professor of Hematology and director of the Myeloma Unit at the University Hospital of Salamanca, to discuss the FDA approval of the subcutaneous daratumumab formulation in multiple myeloma.

On May 1, 2020, the FDA approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adult patients with newly diagnosed or relapsed/refractory multiple myeloma. This new product allows for subcutaneous dosing of daratumumab. The approval is based on findings from the phase 3 COLUMBA (MMY3012) study, which demonstrated noninferiority in terms of efficacy compared with the intravenous (IV) formulation of the CD38-targeted monoclonal antibody.

Results showed that the objective response rate (ORR) was 41.1% with subcutaneous daratumumab versus 37.1% with the IV formulation, thus meeting the criteria for noninferiority.

The median duration per infusion dropped from more than 3 hours per infusion in the IV arm to 5 minutes with the subcutaneous version.

Moreover, the subcutaneous version led to a reduction in treatment burden when compared with the standard version.

Regarding safety in the COLUMBA trial, significantly fewer infusion-related reactions (IRR) were observed in patients who received the subcutaneous formulation versus those who received the IV formulation. The median time to onset of IRR was 1.5 hours in the IV group versus 3.6 hours for the subcutaneous arm. With the exception of IRRs, which primarily occurred with the first dose, the safety profile was similar between the formulations. The rate of grade 3/4 neutropenia was higher in the subcutaneous group compared with the IV group, at 13% versus 8%, respectively. The rates of any grade chills and dyspnea were lower in the subcutaneous group versus IV, likely due to a reduction in IRRs.

The approval is also supported by results from the ongoing, phase 2 PLEIADES (MMY2040) trial (NCT03412565), which adult patients with newly diagnosed myeloma received subcutaneous daratumumab in combination with either bortezomib (Velcade), lenalidomide (Revlimid) and dexamethasone (D-VRd) or bortezomib, melphalan, and prednisone (D-VMP). Patients with relapsed/refractory disease received subcutaneous daratumumab plus lenalidomide/dexamethasone (D-Rd).

Results showed that the ORR in the D-VMP cohort was 88.1%. The ORR was 90.8% for the D-Rd arm and 97% for the D-VRd arm. According to the FDA, the recommended dose of daratumumab and hyaluronidase-fihj is 1800 mg of daratumumab and 30,000 units of hyaluronidase administered subcutaneously into the abdomen over approximately 3 to 5 minutes according to the recommended schedule.

In our exclusive interview, Dr. Mateos discussed the data that led to the approval of the subcutaneous daratumumab formulation and the clinical implications of the regulatory decision.