Darzalex Faspro (daratumumab and hyaluronidase-fihj) for high-risk smoldering multiple myeloma

Initial US Approval:

2020

Key Clinical Studies:

AQUILA (NCT03301220)

Drug Class/Description:

Combination of CD38-directed cytolytic antibody with an endoglycosidase

Indications and Usage:

DARZALEX FASPRO is a combination of daratumumab, a CD38-directed cytolytic antibody, and hyaluronidase, an endoglycosidase, indicated for the treatment of adult patients with: 

• multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant 
• multiple myeloma in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
• multiple myeloma in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
• multiple myeloma in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
• multiple myeloma in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
• multiple myeloma in combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor 
• multiple myeloma in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• multiple myeloma as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
• high-risk smoldering multiple myeloma as monotherapy
• light chain (AL) amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone in newly diagnosed patients. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)

Limitations of Use:

• DARZALEX FASPRO is not indicated and is not recommended for the treatment of patients with light chain (AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials

Dosage and Administration:

For subcutaneous use only.

• Pre-medicate with a corticosteroid, acetaminophen and a histamine-1 receptor antagonist.
• The recommended dosage of DARZALEX FASPRO is (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously into the abdomen over approximately 3 to 5 minutes according to recommended schedule.
• Administer post-medications as recommended. 

Dosage Forms and Strengths:

• Injection: 1,800 mg daratumumab and 30,000 units hyaluronidase per 15 mL (120 mg and 2,000 units/mL) solution in a single-dose vial 

Contraindications:

Patients with a history of severe hypersensitivity to daratumumab, hyaluronidase or any of the components of the formulation.

Warnings and Precautions:

• Hypersensitivity and Other Administration Reactions: Permanently discontinue DARZALEX FASPRO for life-threatening reactions.
• Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis: Monitor patients with cardiac involvement more frequently for cardiac adverse reactions and administer supportive care as appropriate.
• Infections: DARZALEX FASPRO can cause serious and fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. 
• Neutropenia: Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO to allow recovery of neutrophils. 
• Thrombocytopenia: Monitor complete blood cell counts periodically during treatment. Consider withholding DARZALEX FASPRO to allow recovery of platelets.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception.
• Interference with cross-matching and red blood cell antibody screening: Type and screen patients prior to starting treatment. Inform blood banks that a patient has received DARZALEX FASPRO.

Adverse Reactions:

• The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-VRd are peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash. 
• The most common adverse reaction (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO monotherapy is upper respiratory tract infection. 
• The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-VMP are upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain. 
• The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-Rd are fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea. 
• The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-Pd are fatigue, pneumonia, upper respiratory tract infection, and diarrhea. 
• The most common adverse reactions (≥20%) in patients with multiple myeloma who received DARZALEX FASPRO-Kd are upper respiratory tract infection, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral. 
• The most common adverse reactions (≥20%) in patients with high-risk smoldering multiple myeloma who received DARZALEX FASPRO monotherapy are upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, sleep disorder, sensory neuropathy, and injection site reactions.
• The most common adverse reactions (≥20%) in patients with light chain (AL) amyloidosis are upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea, and cough. 
• The most common (≥40%) hematology laboratory abnormalities with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. 

Adapted From:

https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf

 

Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.