What is Darzalex?
Darzalex, also known as daratumumab, is the first monoclonal antibody approved for use in multiple myeloma. Darzalex is made by Janssen Biotech.
How is Darzalex used?
Darzalex is a monoclonal antibody. For the treatment of patients with multiple myeloma, Darzalex is approved for use in the following ways:
What types of patients can benefit from Darzalex?
Darzalex has been studied in patients with newly diagnosed multiple myeloma and in those with relapsed and/or refractory myeloma. Studies of Darzalex as a myeloma treatment have included the following patient populations:
How does Darzalex work?
Darzalex binds to CD38, a protein found on myeloma cells (this protein is also found on other cells, such as red blood cells). It is thought to slow myeloma cell growth in several ways, including by helping the immune system to seek and destroy myeloma cells.
How is Darzalex administered?
Newly Diagnosed Multiple Myeloma
Darzalex may be given as an intravenous (IV) infusion in combination with VMP for newly diagnosed multiple myeloma. It is typically given at a dose of 16 mg/kg of body weight and administered weekly during weeks 1 through 6, every three weeks during weeks 7 to 54, and every 4 weeks until disease progression.
Relapsed/Refractory Multiple Myeloma
Darzalex may be given by itself or in combination with low-dose dexamethasone and either Revlimid or Pomalyst (pomalidomide, Celgene) to treat relapsed/refractory multiple myeloma. When given in combination with other drugs, Darzalex is given as an IV infusion at a dose of 16 mg/kg of body weight and is administered weekly during weeks 1 through 8, every two weeks during weeks 9 through 24, and then every 4 weeks until disease progression.
Darzalex may also be given in combination with Velcade and dexamethasone for relapsed/refractory multiple myeloma. In this combination, Darzalex is administered weekly during weeks 1 through 9, every three weeks during weeks 10 to 24, and every 4 weeks until disease progression.
Before receiving Darzalex, patients should take antihistamines, fever-reducing agents, and steroids to reduce the risk of infusion reactions. The first prescribed dose at week 1 may be split over two consecutive days to minimize infusion reactions (8 mg/kg on Day1 and Day 2). Following the infusion of Darzalex, patients also receive a steroid to reduce the risk of delayed infusion reactions.
Patients receiving Darzalex also receive antiviral medication to prevent shingles, a viral infection that causes a painful rash and is due to a reactivation of the virus that causes chickenpox (herpes zoster virus).
What are Darzalex side effects?
In clinical studies, the most common side effects seen with Darzalex included:
The most common serious side effects include low lymphocyte, red blood cell, neutrophil, and platelet counts.
In clinical trials, severe infusion reactions, such as spasms of the muscles in the major airways of the lung, low oxygen levels, difficulty breathing, and high blood pressure, have been seen with Darzalex. For this reason, patients receive antihistamines, fever-reducing agents, and steroids before infusion of Darzalex to reduce the risk of infusion reactions. Following the infusion of Darzalex, patients also receive an oral corticosteroid to reduce the risk of delayed infusion reactions.
How are side effects of Darzalex managed?
Patients who experience an infusion reaction have their Darzalex infusion stopped and their symptoms treated. After symptoms resolve, the infusion may be resumed at a slower rate. Darzalex is discontinued in patients who experience a life-threatening infusion reaction or multiple severe reactions.
Can Darzalex affect laboratory testing?
Because Darzalex binds to CD38 on red blood cells, it may interfere with testing performed for blood transfusions. As a result, patients should be typed and screened prior to beginning treatment with Darzalex.
Because it is a monoclonal antibody, Darzalex can be detected in tests used to monitor M protein and thus may affect the determination of complete response and disease progression in some patients with certain types of myeloma.
What have Darzalex clinical trials shown?
The efficacy of Darzalexin combination with VMP in patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplant was shown in a phase 3 clinical trial (ALCYONE), in which 706 patients participated. All patients received VMP; one half of the patients also received IV Darzalex at 16 mg/kg (D-VMP).
The ALCYONE study showed the following:
The safety and efficacy of Darzalex was demonstrated in two phase 1/2 clinical trials in heavily pre-treated patients with relapsed and/or refractory myeloma.
The SIRIUS study included 106 patients who had received at least three prior therapies, including a proteasome inhibitor and an IMiD, or who were refractory to both a proteasome inhibitor and an IMiD. Patients received IV Darzalex at a dose of 16 mg/kg.
The SIRIUS study showed the following:
The GEN501 study evaluated different doses of Darzalex in patients who had received at least two prior therapies. Thirty patients received IV Darzalex at a dose of 8 mg/kg and 42 patients received IV Darzalex at a dose of 16 mg/kg. In patients receiving the 16 mg/kg dose:
The promising results of these studies supported the approval of Darzalex for use as a multiple myeloma treatment. Darzalex is currently listed as one of several preferred regimens for previously treated myeloma in current treatment guidelines.
The CASTOR study included 498 patients with relapsed or refractory multiple myeloma who had received at least one previous line of therapy and had at least a partial response to one or more of their previous therapies. Patients received either Darzalex in combination with Velcade and dexamethasone (DVd;251 patients) or Velcade with dexamethasone (Vd; 247 patients).
The CASTOR study showed the following:
The POLLUX study included 569 patients with relapsed or refractory multiple myeloma who had received one or more previous lines of therapy. Patients received either Darzalex, Revlimid and dexamethasone (DRd; 286 patients) or Revlimid and dexamethasone (Rd; 283 patients).
The POLLUX study showed the following:
What other Darzalex combinations have been evaluated?
Darzalex is being evaluated in an ongoing multicenter phase 1b study (MMY 1001; NCT01998971) in combination with various myeloma therapies in newly diagnosed and relapsed and/or refractory myeloma.
How is Darzalex currently being studied in myeloma?
Darzalex is being evaluated as part of the phase 1/2 MyDRUG trial (NCT02884102). Patients with certain genetic abnormalities will receive Darzalex in combination with Ninlaro (ixazomib, Takeda Oncology), Pomalyst, and dexamethasone. The genetic sequencing of the patient’s tumor is required via enrollment in the MMRF002 Molecular Profiling Protocol study (NCT02884102)
Darzalex is being evaluated in several phase 3 studies in the United States.
In relapsed and/or refractory myeloma:
In newly diagnosed myeloma:
Interested in learning more about Darzalex clinical trials? Talk to an MMRF Nurse Patient Navigator to learn more or use our clinical trials finder:
Updated February 2019
Please visit the sponsor’s official patient site for up-to-date information on Darzalex