FDA Approves Subcuteanous Daratumumab with Carfilzomib, Dexamethasone for Patients With Multiple Myeloma

The US Food and Drug Administration (FDA) has announced the approval of daratumumab and hyaluronidase-fihj (DARZALEX FASPRO) in combination with carfilzomib (Kyprolis) and dexamethasone (Kd) for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received 1 - 3 prior lines of therapy.

The approval, granted to the Janssen Pharmaceutical Companies of Johnson & Johnson, has followed the regulatory submission to the FDA in January of this year.

PLEIADES Study

The approval noted updated data from the PLEIADES study presented at the 2020 American Society of Hematology (ASH) Annual meeting as being pivotal to the approval.

The PLEIADES study is a currently ongoing Phase 2 non-randomized, open-label trial evaluating the clinical benefit of daratumumab and hyaluronidase-fihj in combination with 4 standard-of-care treatment regimens in patients with multiple myeloma.

It is evaluating daratumumab and hyaluronidase-fihj in transplant-eligible newly diagnosed multiple myeloma (NDMM), transplant-ineligible nDMM, relapsed refractory multiple myeloma (RRMM) with more than a single prior line of therapy, and RRMM with a single prior line of therapy and exposure to lenalidomide.

Data from the study demonstrated response rates of daratumumab and hyaluronidase-fihj and dexamethasone were similar to results of daratumumab and dexamethasone from the Phase 3 CANDOR study. CANDOR supported the first-ever approval of an anti-CD38 monoclonal antibody in combination with carfilzomib.

In a statement, Ajai Chari, MD, Director of Clinical Research in the Multiple Myeloma Program and Associate Director of Clinical Research, Mount Sinai Cancer Clinical Trials Office noted additional treatment combinations supported by PLEIADES data may influence the course of the disease progression.

"The approval of subcutaneous daratumumab in combination with Kd will help clinicians address unmet patient needs by reducing the administration time from hours to just minutes, and reducing the frequency of infusion-related reactions, as compared to the intravenous daratumumab formulation in combination with Kd,” he said.

Safety Profile

Data show the safety profile of the daratumumab and hyaluronidase-fihj plus carfilzomib and dexemthasone regim had consistent outcomes with the safety profiles of daratumumab and hyaluronidase-fihj, carfilzomib, and dexamethasone.

There were serious adverse events reported in 27% of patients receiving the combination treatment. The most common adverse events reported (≥20%) were upper respiratory tract infection, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea and peripheral edema. Additionally, fatal adverse reactions occurred in 3% of patients.

Craig Tendler, MD, Global Head of Late Development, Diagnostics & Medical Affairs, Hematology & Oncology, Janssen Research & Development, discussed in a statement the company’s continued goal to work to transform patient outcomes in the treatment of multiple myeloma.

"Today's approval of DARZALEX FASPRO, in combination with yet another widely used regimen, further substantiates the subcutaneous formulation as a foundational element in the treatment of multiple myeloma," Tendler said. "We will continue to explore the full potential of DARZALEX FASPRO as part of our commitment to advancing science and transforming patient outcomes in the treatment of this disease."