Since the U.S. Food and Drug Administration (FDA) approval of DARZALEX® (daratumumab) in 2015, the first CD38-directed antibody to treat multiple myeloma has been used in the treatment of more than 68,000 patients in the U.S. alone.
Since the U.S. Food and Drug Administration (FDA) approval of DARZALEX® (daratumumab) in 2015, the first CD38-directed antibody to treat multiple myeloma has been used in the treatment of more than 68,000 patients in the U.S. alone.1 Nearly five years later, the U.S. FDA approved DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in May 2020, a subcutaneous formulation of daratumumab for the treatment of multiple myeloma. DARZALEX FASPRO® follows as the only subcutaneous CD38-directed antibody approved across six indications in the front line and relapsed or refractory settings.
The fixed-dose formulation of daratumumab is administered in approximately three to five minutes, significantly less time than the original intravenous formulation, which is administered over several hours.
The approval of DARZALEX FASPRO® was supported by findings from the Phase 3 COLUMBA (MMY3012) non-inferiority study, which showed a comparable overall response rate between patients with relapsed or refractory multiple myeloma who have received three or more prior lines of therapy taking DARZALEX FASPRO® monotherapy compared with those taking intravenous DARZALEX® monotherapy (41 percent vs 37 percent, respectively) in patients in the third line of treatment or later. The co-primary endpoint of remaining therapeutic drug concentration (maximum Ctrough) of DARZALEX FASPRO® was also non-inferior to intravenous DARZALEX®. Findings from the study additionally demonstrated a nearly two-thirds reduction in systemic administration-related reactions (13 percent vs. 34 percent, respectively). Safety was found to be generally consistent with intravenous DARZALEX®.2
The approval was also based on cross-study comparisons from the Phase 2 PLEIADES study (MMY2040), which demonstrated that DARZALEX FASPRO® showed comparable clinical activity to several intravenous DARZALEX® regimens, when used in combination with standard-of-care treatment regimens, such as bortezomib, melphalan and prednisone in newly diagnosed transplant-ineligible multiple myeloma and lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, who had failed at least one prior therapy.3
“The approval of subcutaneous daratumumab marks an important next step, providing comparable efficacy to intravenous daratumumab for approved indications spanning a wide range of newly diagnosed or relapsed and refractory multiple myeloma,” said Saad Z. Usmani, M.D., Division Chief of Plasma Cell Disorders at Levine Cancer Institute. “In clinics like mine, patients may benefit from the three to five-minute injection and the nearly three times fewer systemic administration-related reactions compared to the intravenous formulation.”
DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation. Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (e.g., anaphylactic reactions) to daratumumab or any of the components of the formulation. DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. See Important Safety Information below.
With DARZALEX FASPRO®, researchers worked to provide patients and providers with a different treatment experience for multiple myeloma patients across approved indications. Many patients will be able to receive subcutaneous administration starting with their first dose.
DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) [Halozyme's ENHANZE® drug delivery technology]. The intravenous DARZALEX® formulation remains available as an option for patients and their physicians.
The U.S. FDA approval of DARZALEX FASPRO® marks the first approval for this innovative subcutaneous formulation globally, and Janssen continues to work with health authorities around the world in an effort to bring this new treatment option to patients living with multiple myeloma.
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
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
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
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
IMPORTANT SAFETY INFORMATION
DARZALEX FASPRO® is contraindicated in 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
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®.
In a pooled safety population of 683 patients with multiple myeloma (N=490) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 10% of patients experienced a systemic administration-related reaction (Grade 2: 3.5%, Grade 3: 1%). Systemic administration-related reactions occurred in 9% of patients with the first injection, 0.4% with the second injection, and cumulatively 0.8% with subsequent injections. The median time to onset was 3.2 hours (range: 9 minutes to 3.5 days). Of the 117 systemic administration-related reactions that occurred in 66 patients, 100 (85%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in less than 1% of the patients.
Severe reactions included hypoxia, dyspnea, hypertension, and tachycardia. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, and hypotension.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.
In this pooled safety population, injection-site reactions occurred in 9% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 4.7 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management.
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.
Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.
The combination of DARZALEX FASPRO® with lenalidomide or thalidomide is contraindicated in pregnant women because lenalidomide and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide or thalidomide prescribing information on use during pregnancy.
Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.
Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.
Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.
In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, pyrexia, cough, muscle spasms, back pain, vomiting, upper respiratory tract infection, peripheral sensory neuropathy, constipation, and pneumonia.
The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.
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