Darzalex™

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:

  • For newly diagnosed patients who are who are not eligible for a stem cell transplant
    • In combination with Velcade (bortezomib, Takeda Oncology), melphalan, and prednisone (D-VMP) 
    • In combination with Velcade, Thalomid (thalidomide, Celgene), and dexamethasone (D-VTd)
    • In combination with Revlimid (lenalidomide, Celgene) and dexamethasone (DRd) 
  • For relapsed or refractory patients
    • In combination with Revlimid  and dexamethasone, or Velcade and dexamethasone, in patients who have received at least one prior therapy 
    • Alone in patients who have received at least three prior therapies, including a proteasome inhibitor and an immunomodulatory agent (IMiD), or who did not respond to a proteasome inhibitor and IMiD

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:

    • Patients who are not eligible for a stem cell transplant
    • Patients who have received several prior therapies (heavily pre-treated)
    • Patients who were refractory to both proteasome inhibitors and IMiDs
    • Patients who previously received high-dose chemotherapy and stem cell transplant
    • Patients with reduced kidney function (renal impairment)
    • Patients with mildly reduced liver function (mild hepatic impairment)

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, VTd, or Rd for newly diagnosed multiple myeloma. The recommended dose of Darzalex is 16 mg/kg of body weight.

In the D-VMP regimen, Darzalex is administered weekly during weeks 1 through 6, every three weeks during weeks 7 to 54, and every 4 weeks until disease progression.

In the D-VTd regimen, Darzalex is administered weekly during weeks 1 through 8, every two weeks during weeks 9 to 16 during induction and then every two weeks for 8 weeks during consolidation.

In the DRd regimen, Darzalex is administered weekly during weeks 1 and 2, every two weeks during weeks 3 and 6, and then every four weeks during week 7 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:

  • Infusion reactions
  • Low platelet counts (thrombocytopenia)
  • Low numbers of white blood cells known as neutrophils (neutropenia)
  • Fatigue
  • Nausea, diarrhea, constipation, or vomiting
  • Back pain or joint pain
  • Muscle spasms
  • Fever, chills, dizziness, or insomnia
  • Cough
  • Shortness of breath
  • Swelling in hands or lower legs
  • Numbness, prickling, or tingling in hands and feet (peripheral sensory neuropathy)
  • Upper respiratory infection

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 Darzalex in 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 overall response rate was 90.9% in the D-VMP group vs 73.9% in the VMP group. The rate of complete response or better was 42.6% in the D-VMP group vs 24.4% in the VMP group.
  • Responses lasted at least 18 months for 71.6% of the D-VMP group vs 50.2% for the VMP group.
  • 22.3% of patients in the D-VMP group achieved MRD negative status, vs 6.2% in the VMP group.
  • Most common side effects were low blood counts (anemia, neutropenia, thrombocytopenia) and infection.
  • Infusion reactions were observed in 28.0% of patients.

The efficacy of Darzalex in combination with VTd in patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplant was shown in a phase 3 clinical trial (CASSIOPEIA), in which 1,085 patients participated. All patients received VTd; one half of the patients also received IV Darzalex at 16 mg/kg (D-VTd).

The CASSIOPEIA study showed the following:

  • 39% patients in the D-VTd group vs 26% in the VTd group achieved a complete response or better, and 64% vs 44% achieved minimal residual disease negative status.

The efficacy of Darzalex in combination with Rd  in patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplant was shown in a phase 3 clinical trial (MAIA), in which 737 patients participated. All patients received Rd; one half of the patients also received IV Darzalex at 16 mg/kg (DRd).

The MAIA study showed the following:

  • The percentage of patients with a complete response or better was 47.6% for those treated with DRd and 24.9% patients treated with Rd. 
  • The percentage of patients who were alive without disease progression (at 30 months) was 70.6% for those treated with DRd and 55.6% for those treated with Rd.
  • A total of 24.2% of the patients treated with DRd, as compared with 7.3% of the patients treated with Rd achieved MRD negative status.

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:

  • Patients had received an average of five prior lines of therapy.
  • The overall response rate was 29.2%, with 2.8% of patients achieving a stringent complete response and 9.4% achieving a very good partial response.
  • More than half of patient responses lasted 7.4 months or more..
  • The estimated time that patients lived without disease progression was 3.7 months. 
  • 65% of patients were alive at 1 year.
  • At a subsequent cut-off, overall survival was 17.5 months.
  • Infusion reactions were seen in 42% of patients; most were mild or moderate.
  • The most common side effects included fatigue, low blood count (anemia), nausea, low platelet counts (thrombocytopenia), low neutrophil counts (neutropenia), back pain, and cough.
  • The most common severe side effects were low platelet count (thrombocytopenia), low red blood cell count (anemia), and low neutrophil count (neutropenia).

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:

  • More than half had received four prior lines of therapy or more .
  • The overall response rate was 36%, including one complete response and three very good partial responses.
  • The estimated time that patients lived without disease progression was 5.6 months.
  • 65% of patients who responded to therapy did not have disease progression at 1 year.
  • 77% of patients were alive at 1 year.
  • Infusion reactions were seen in 71% of patients; most were mild or moderate.
  • The most common side effects included fatigue, hay fever, and fever.
  • The most common severe side effects were pneumonia and low platelet counts.

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:

  • Patients had received an average of 2 prior lines of therapy
  • The overall response rate was 82.9% in the DVd group vs. 63.2% in the Vd group
  • The median progression free survival was not reached in the DVd group (after an average follow up of 7.4 months) and was 7.2 months in the Vd group
  • Patients in DVd group had a 61% reduction in the risk of disease progression or death compared to the Vd group.  
  • The most common side effects for those in the DVd group were low blood count (anemia), low platelet count (thrombocytopenia), numbness pain or tingling of hands and feet (peripheral sensory neuropathy), diarrhea upper respiratory infection, fatigue and cough.
  • The most common severe side effects for those in the DVd group were low red blood count (anemia), low platelet count (thrombocytopenia),low white blood cell count (neutropenia, lymphopenia), pneumonia, and high blood pressure.

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:

  • Patients received an average of 1 prior line of therapy
  • The overall response rate was 92.9% for the DRd group vs 76.4% for the Rd group
  • The median progression free survival was not reached in the DRd group (after an average follow up of 13.5 months) and was 18.4 months in the Rd group
  • Patients in DRd group had a 63% reduction in the risk of disease progression or death compared to the Rd group.  
  • The most common side effects for those in the DRd group were low red blood count (anemia), low platelet count (thrombocytopenia),low white blood cell count (neutropenia), fatigue, nausea, diarrhea, constipation, cough, muscle spasms, upper respiratory infection, cold symptoms, and fever.
  • The most common severe side effects for those in the DRd group were low red blood count (anemia), low platelet count (thrombocytopenia),low white blood cell count (neutropenia, lymphopenia), fever from low white blood cell count (febrile neutropenia), diarrhea, fatigue, and pneumonia 

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:

  • Darzalex, Kyprolis (carfilzomib, Amgen) and dexamethasone (CANDOR; NCT03158688)
  • Subcutaneous (that is, under the skin) versus IV administration (NCT03277105)

In newly diagnosed myeloma:

  • In combination with Velcade, Revlimid, and dexamethasone (NCT03652064) for patients for whom autologous stem cell transplantation is not planned.

Interested in learning more about Darzalex clinical trials? Talk to an MMRF Nurse Patient Navigator to learn more or use our clinical trials finder:

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Updated  February 2019

Please visit the sponsor’s official patient site for up-to-date information on Darzalex