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 and Genmab.


How is Darzalex used?

Darzalex™ (daratumumab, Janssen/Genmab) is a monoclonal antibody. It is approved for use in the treatment of multiple myeloma patients:

  • In combination with the medicines Velcade, Melphalan, and Prednisone (VMP) for treatment of newly diagnosed multiple myeloma patients who are not eligible for a stem cell transplant
  • In combination with the medicines lenalidomide and dexamethasone, or bortezomib and dexamethasone, in people who have received at least one prior medicine to treat multiple myeloma.
  • Alone in people who have received at least three prior medicines to treat multiple myeloma, including a proteasome inhibitor and an immunomodulatory agent, or who did not respond to a proteasome inhibitor and an immunomodulatory agent.

What types of patients can benefit from Darzalex?

Darzalex has been studied in newly diagnosed patients and also in patients with relapsed and/or refractory myeloma including:

    • Patients who are not eligible for a stem cell transplant
    • Patients who have received several prior therapies (heavily pretreated)
    • 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 marker found on the surface of myeloma cells. It is thought to inhibit myeloma cell growth in several ways, including by directly affecting myeloma cells and by enabling immune cells to kill myeloma cells.


How is Darzalex administered?

Darzalex™ (daratumumab, Janssen/Genmab) is given as an intravenous (IV) infusion into a vein. It is typically given 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.

Before receiving Darzalex, patients receive premedication with antihistamines, fever-reducing agents, and steroids to reduce the risk of infusion reactions. Following the infusion of Darzalex, patients also receive a steroid to reduce the risk of delayed infusion reactions.

Patients receiving Darzalex also receive 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™ (daratumumab, Janssen/Genmab) included:

  • Infusion reactions
  • Fatigue
  • Nausea
  • Back pain
  • Fever
  • Cough
  • Upper respiratory infection
  • The most common serious side effects included 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 premedication with 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 a steroid to reduce the risk of delayed infusion reactions.

How are side effects of Darzalex managed?
Patients who experience an infusion reaction will have their Darzalex infusion stopped and their symptoms treated. After symptoms resolve, the infusion may be resumed at a slower rate. Darzalex will be discontinued in patients who experience a life-threatening infusion reaction or multiple severe reactions.

Can Darzalex affect laboratory testing?
Because Darzalex binds to the CD38 marker 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.

As Darzalex is an IgG monoclonal antibody, it can be detected on tests used for the clinical monitoring of M protein and may impact the determination of complete response and of disease progression in some patients with IgG myeloma


What have Darzalex clinical trials shown?

The efficacy of Darzalex™ (daratumumab, Janssen/Genmab) in combination with Velcade, Melphalan, and Prednisone in newly diagnosed patients who are not eligible for stem cell transplant was shown in a phase III clinical trial. The ALCYONE study included 706 patients who were newly diagnosed with multiple myeloma but not eligible for stem cell transplant due to age or frailty. All patients received Velcade, Melphalan, and Prednisone (VMP); one half of the patients also received IV Darzalex at 16 mg/kg (D-VMP).

  • The overall response rate was 90.0% in the D-VMP group vs 73.9% in the VMP group. The rate of CR 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% of the VMP group.
  • 22.4% 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 and infection.
  • Infusion reactions were observed in 27.7% of patients.

The safety and efficacy of Darzalex™ (daratumumab, Janssen/Genmab) was demonstrated in two Phase 1/2 clinical trials in heavily-pretreated relapsed and/or refractory myeloma. The SIRIUS study included 106 patients who had received at least 3 prior therapies, including a proteasome inhibitor and an IMiD, or who were refractory to both a proteasome inhibitor and an IMiD. Patients received intravenous (IV) Darzalex at a dose of 16 mg/kg.

  • Patients has received an average of 5 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 (VGPR).
  • Responses lasted an average of 7.4 months.
  • 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 43% of patients and most were mild or moderate in nature.
  • The most common side effects included fatigue, anemia, nausea, and low platelet counts.
  • The most common severe side effects were low platelet, red blood cell, and neutrophil counts.

The GEN501 study evaluated different doses of Darzalex in patients who had received at least 2 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:

  • Patients had received an average of 4 prior lines of therapies.
  • The overall response rate was 36%, including 1 complete response (CR) and 3 VGPR.
  • 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 and most were mild or moderate in nature.
  • 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, and Darzalex is listed as one of several preferred regimens for previously treated myeloma in current treatment guidelines.

What other Darzalex combinations have been evaluated?

Darzalex is being evaluated in an ongoing multicenter Phase Ib study (MMY 1001) in combination with various myeloma therapies in newly diagnosed and relapsed and/or refractory myeloma.

  • In newly diagnosed patients, preliminary results show that Darzalex in combination frontline regimens such as Velcade® (bortezomib, Takeda)-dex, Velcade-Thalomid® (thalidomide, Celgene)-dex, or Velcade-melphalan-dex was well tolerated with encouraging efficacy.
  • In heavily pretreated patients, the combination of Darzalex and Pomalyst-dex resulted in a high 71% overall response rate.

How is Darzalex currently being studied in myeloma?

Darzalex is being evaluated when added to various combination therapies in four Phase 3 studies in the United States.

In relapsed and/or refractory myeloma, Darzalex is being evaluated in two fully-enrolled trials:

  • In combination with Revlimid® (lenalidomide, Celgene), and dexamethasone.
  • In combination with Velcade® (bortezomib, Takeda Oncology) and dexamethasone.

In newly diagnosed myeloma, Darzalex is being evaluated:

  • In combination with Revlimid® (lenalidomide, Celgene), and dexamethasone. LEARN MORE
  • In combination with Velcade, melphalan, and prednisone. LEARN MORE

Single-agent Darzalex is also being made available as part of an expanded access program (EAP) study for patients with relapsed and/or refractory myeloma. The Multiple Myeloma Research Consortium (MMRC) is currently collaborating with Janssen on this study, which provides access to Darzalex treatment for patients who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD®, Celgene) or whose disease is refractory to both a PI and an IMiD, and who are not eligible for or who do not have access to enrollment in another Darzalex study. LEARN MORE

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

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