Darzalex FASPRO (the subcutaneous shot of daratumumab) has received its ninth FDA approval, this time with use in combination with carfilzomib and dexamethasone for relapsed or refractory myeloma patients who have received 1-3 prior lines of therapy.

The approval was based on updated study PLEIADES study data presented at the 2020 ASH meeting which showed that Darzalex FASPRO and carfilzomib/dex results were similar to the Darzalex IV and carfilzomib/dex results from the Phase III CANDOR study. The study showed an overall response rate of 84.4% and 77.3% of patients achieving at least a very good partial response or better. 

Ajai Chari, MD and Director of Clinical Research in the Multiple Myeloma program at Mount Sinai said: 

“Data from the PLEIADES trial continue to support additional treatment combinations that can influence the course of this disease as early as after the first relapse by providing durable responses that may help to delay 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.”  

The safety profile of the subcutaneous administration with carfilzomib and dex was similar to the IV formulation. The most common side effects (greater than 20%) were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, difficulty breathing, headache, fever, nausea and swelling in the hands or feet. Fatal side effects occurred in 3% of patients. 

Additional prior approvals include Darzalex FASPRO: 

• in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
• in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
• in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
• in combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
• in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
• in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• as monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent

Darzalex FASPRO^® is also temporarily approved in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed AL amyloidosis patients. This approval is contingent on future studies confirming the response rate from the early accelerated approval. Note: It is not approved or recommended for the treatment of patients with AL amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.