What is Darzalex/Darzalex Faspro™?
Darzalex, also known as daratumumab, is the first monoclonal antibody approved for use in multiple myeloma. Darzalex Faspro is a combination of daratumumab and hyaluronidase. Both drugs are made by Janssen Biotech.

How is Darzalex/Darzalex Faspro used?
Darzalex is a monoclonal antibody and can be administered to patients in two different ways: (1) as an intravenous (IV) infusion [Darzalex], or (2) as a subcutaneous (SC) injection (that is, under the skin) [Darzalex Faspro].For the treatment of patients with multiple myeloma, Darzalex is approved for use in the following ways:
- For newly diagnosed patients who are not eligible for a stem cell transplant:
- In combination with Velcade (bortezomib, Takeda Oncology), melphalan and prednisone (D-VMP)
- In combination with Revlimid (lenalidomide, Celgene) and dexamethasone (DRd)
- For newly diagnosed patients who are eligible for a stem cell transplant:
- In combination with Velcade, Thalomid (thalidomide, Celgene) and dexamethasone (D-VTd)
- For relapsed or refractory patients:
- In combination with Revlimid and dexamethasone (DRd), or Velcade and dexamethasone (DVd), in patients who have received at least one prior therapy
- In combination with Kyprolis (carfilzomib, Amgen) and dexamethasone (DKd) in patients who have received one to three prior lines of therapy
- In combination with Pomalyst (pomalidomide, Celgene) and dexamethasone (DPd) in patients who have received at least two prior therapies including Revlimid and a proteasome inhibitor
- Alone in patients who have received at least three prior therapies, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who did not respond to a PI and IMiD
- For newly diagnosed patients who are who are not eligible for a stem cell transplant:
- In combination with Velcade, melphalan and prednisone (D-VMP)
- In combination with Revlimid and dexamethasone (DRd)
- For relapsed or refractory patients:
- In combination with Revlimid and dexamethasone (DRd), or Velcade and dexamethasone (DVd), in patients who have received at least one prior therapy
- Alone in patients who have received at least three prior therapies, including a PI and an IMiD, or who are double-refractory to a PI and an IMiD
What types of patients can benefit from Darzalex/Darzalex Faspro?
Darzalex/Darzalex Faspro has been studied in patients with newly diagnosed multiple myeloma and in those with relapsed and/or refractory myeloma. Studies of Darzalex/Darzalex Faspro 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 PIs 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/Darzalex Faspro work?
Darzalex/Darzalex Faspro 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/Darzalex Faspro administered?
IV FormulationDarzalex may be given as an IV infusion in combination with Velcade, melphalan, and prednisone (D-VMP), Velcade, Thalomid (thalidomide, Celgene), and dexamethasone (D-VTd), or Revlimid and dexamethasone (DRd) 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 3 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 2 weeks during weeks 9 to 16 during induction and then every 2 weeks for 8 weeks during consolidation.
- In the DRd regimen, Darzalex is administered weekly during weeks 1 and 2, every 2 weeks during weeks 3 and 6, and then every 4 weeks during week 7 until disease progression.
- For regimens where Darzalex is given by itself or in combination with low-dose dexamethasone and either Revlimid or Pomalyst, Darzalex is administered weekly during weeks 1 through 8, every 2 weeks during weeks 9 through 24, and then every 4 weeks until disease progression.
- In the DVd regimen, Darzalex is administered weekly during weeks 1 through 9, every 3 weeks during weeks 10 to 24, and every 4 weeks until disease progression.
- For the DKd regimen, Darzalex is administered on days 1 and 2 of the first week at a dose of 8 mg/kg of body weight. The remaining schedule uses a dose of 16 mg/kg every week during weeks 2 to 8, every 2 weeks during weeks 9 to 24, and then every 4 weeks until disease progression.
The recommended dose of Darzalex Faspro is 1,800 mg/30,000 units administered subcutaneously over approximately 3 to 5 minutes.
- When used alone or in combination with Revlimid and dexamethasone, Darzalex Faspro is administered weekly during weeks 1 through 8, every 2 weeks during weeks 9 to 24 and every 4 weeks until disease progression.
- When combined with VMP, Darzalex Faspro is administered weekly during weeks 1 through 6, every 3 weeks during weeks 7 to 54 and then every 4 weeks until disease progression.
- When combined with Velcade and dexamethasone, Darzalex Faspro is administered weekly during weeks 1 through 9, every 3 weeks during weeks 10 to 24 and then every 4 weeks until disease progression.
Patients receiving Darzalex/Darzalex Faspro 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/Darzalex Faspro 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
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.
In clinical studies, the most common side effects seen with Darzalex Faspro included:
- Upper respiratory tract infection
- Nausea, diarrhea, constipation or vomiting
- Fatigue
- Fever
- Numbness, prickling or tingling in hands and feet (peripheral sensory neuropathy)
- Cough
- Insomnia
- Back pain
- Muscle spasms
- Pneumonia
- Shortness of breath
- Low platelet counts (thrombocytopenia)
- Low numbers of white blood cells
How are side effects of Darzalex/Darzalex Faspro 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/Darzalex Faspro affect laboratory testing?
Because Darzalex/Darzalex Faspro 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/Darzalex Faspro.Because it is a monoclonal antibody, Darzalex/Darzalex Faspro 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/Darzalex Faspro clinical trials shown?
DarzalexThe 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 minimal residual disease (MRD) negative status vs. 6.2% in the VMP group.
- The most common side effects were low blood counts (anemia, neutropenia, thrombocytopenia) and infection.
- Infusion reactions were observed in 28.0% of patients.
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% for 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.
- 24.2% of the patients treated with DRd, as compared with 7.3% of the patients treated with Rd, achieved MRD-negative status.
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 MRD-negative status.
The SIRIUS study included 106 patients who had received at least three prior therapies, including a PI and an IMiD, or who were refractory to both a PI 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 cutoff, 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).
- 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.
- The most common side effects included fatigue, allergic rhinitis and fever.
- The most common severe side effects were pneumonia and low platelet counts.
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 two 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 the 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 one 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.
The CANDOR study showed the following:
- Patients had received an average of two prior lines of therapy.
- The overall response rate was 84% in the DKd group vs. 75% in the Kd group.
- The median progression-free survival was not reached in the DKd group (after an average follow up of 17 months) and was 15.8 months in the Kd group.
- Patients in the DKd group had a 37% reduction in the risk of disease progression or death compared to the Kd group.
- The most common side effects for those in the DKd group were low platelet count (thrombocytopenia), low red blood cell count (anemia), diarrhea, high blood pressure (hypertension), upper respiratory tract infection, fatigue, and shortness of breath (dyspnea).
- The most common severe side effects for those in the DKd group were pneumonia, fever (pyrexia), influenza, sepsis, anemia, bronchitis, and diarrhea.
The phase 3 COLUMBA study included 522 patients with relapsed or refractory multiple myeloma who had received at least three previous lines of therapy. Patients received Revlimid and dexamethasone with either Darzalex (259 patients) or Darzalex Faspro (263 patients).
The COLUMBA study showed the following:
- Darzalex Faspro was no different than Darzalex with respect to responses and time to disease progression.
- The duration of Darzalex Faspro administration was in minutes compared to hours for Darzalex.
- Infusion-related reactions occurred in 12% of patients receiving Darzalex Faspro compared to 35% receiving Darzalex.
The PLEIADES study showed the following:
- Darzalex Faspro in combination with standard regimens for multiple myeloma has comparable clinical activity and safety relative to corresponding Darzalex regimens.
- Darzalex Faspro was associated with lower infusion-related reactions and shorter durations of administration.
- 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.
- Darzalex is being evaluated as part of the phase 1/2 MyDRUG trial (NCT03732703). 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 Faspro is being evaluated in a phase 2 trial as a treatment for patients who have been previously treated with Darzalex (NCT03871829).
- Darzalex is being evaluated in combination with Velcade, Revlimid, and dexamethasone ( NCT03652064 ) for patients with newly diagnosed myeloma for whom autologous stem cell transplantation is not planned.
Updated September 2020
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