Summary of Clinical Use

Daratumumab was the first anti-CD38 monoclonal to gain clinical approval for the treatment of multiple myeloma (MM). In November 2015, the US FDA granted accelerated approval for daratumumab as a treatment for MM, in patients who have received at least three prior treatments. The EMA granted marketing authorisationfro this indication in 2016. Phase 3 trial NCT02136134 evaluated the addition of daratumumab to bortezomib and dexamethasone in patients with relapsed or refractory MM. Preliminary results showed that this combination was much more effective than the current standard of care (as presented at the 2016 ASCO Annual Meeting, June 3-7, Chicago: Abstract LBA4 and reported in [5]). In November 2016, the FDA approved the use of daratumumab plus lenalidomide and dexamethasone, or bortezomib and dexamethasone for MM patients who have received at least one prior therapy. In Europe the EMA has granted daratumumab orphan designation for the treatment of plasma-cell myeloma (2013) and AL amyloidosis (2018). FDA approval was further expanded in September 2019 to include treatment of newly diagnosed MM in patients who are eligible for autologous stem cell transplant (daratumumab plus bortezomib, thalidomide, and dexamethasone in this instance). Click here to link to ClinicalTrials.gov's listing of daratumumab trials. Darzalex Faspro® (daratumumab plus hyaluronidase-fihj) was FDA approved in May 2020, to allow subcutaneous dosing of daratumumab in indications for which intravenous daratumumab had previously been authorised. In January 2021,Darzalex Faspro® was FDA approved as a treatment for newly diagnosed light chain amyloidosis, a disease that is charactersed by the formation of deposits of IgG light chain proteins that are produced by a clonal population of bone marrow plasma cells, and which often occurs in association with MM.

Mechanism Of Action and Pharmacodynamic Effects

Daratumumab binds the cell surface glycoprotein, CD38, which is highly expressed in hematological malignancies including multiple myeloma. Antibody/CD38 association induces cytotoxic events that lead to death of the malignant cells, in vitro and in vivo [2]. This antibody may improve the antineoplastic activity of other chemotherapy drugs used to treat myeloma [3-4].

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT02136134	Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma	Phase 3 Interventional	Janssen Research & Development, LLC