DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) injection, for subcutaneous use
Brief Summary of Full Prescribing Information
INDICATIONS AND USAGE
DARZALEX FASPRO 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 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.
CONTRAINDICATIONS
DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab,
hyaluronidase or any of the components of the formulation [see Warnings and Precautions and Adverse
Reactions].
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.
Systemic Reactions
In a pooled safety population of 490 patients who received DARZALEX FASPRO as monotherapy or in combination,
11% of patients experienced a systemic administration-related reaction (Grade 2: 3.9%, Grade 3: 1.4%). Systemic
administration-related reactions occurred in 10% of patients with the first injection, 0.2% with the second
injection, and cumulatively 0.8% with subsequent injections. The median time to onset was 3.7 hours (range:
9 minutes to 3.5 days). Of the 84 systemic administration-related reactions that occurred in 52 patients, 73
(87%) 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, pruritis, chills, vomiting, nausea, and hypotension.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids
[see Dosage and Administration (2.3) in Full Prescribing Information]. 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
[see Dosage and Administration (2.3) in Full Prescribing Information].
Local Reactions
In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2
reactions in 0.6%. The most frequent (>1%) injection-site reaction was injection site erythema. These local
reactions occurred a median of 7 minutes (range: 0 minutes to 4.7 days) after starting administration of
DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.
Neutropenia
Daratumumab may increase neutropenia induced by background therapy [see Adverse Reactions].
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.
Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy [see Adverse Reactions].
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.
Embryo-Fetal Toxicity
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 [see
Use in Specific Populations].
The combination of DARZALEX FASPRO with lenalidomide is contraindicated in pregnant women, because
lenalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide 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 [see References]. The determination of a patient’s ABO
and Rh blood type are not impacted [see Drug Interactions].
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
[see Dosage and Administration (2.1) in Full Prescribing Information].
Interference with Determination of Complete Response
Daratumumab is a human 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 [see Drug Interactions]. This interference can impact the determination of complete response
and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
• Hypersensitivity and Other Administration Reactions [see Warning and Precautions].
• Neutropenia [see Warning and Precautions].
• Thrombocytopenia [see Warning and Precautions].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed
in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and
may not reflect the rates observed in practice.
Newly Diagnosed Multiple Myeloma
In Combination with Bortezomib, Melphalan and Prednisone
The safety of DARZALEX FASPRO with bortezomib, melphalan and prednisone (D-VMP) was evaluated in a
single-arm cohort of PLEIADES [see Clinical Studies (14.1) in Full Prescribing Information]. Patients received
DARZALEX FASPRO 1,800 mg/30,000 units administered subcutaneously once weekly from weeks 1 to 6, once
every 3 weeks from weeks 7 to 54 and once every 4 weeks starting with week 55 until disease progression
or unacceptable toxicity (N=67) in combination with bortezomib, melphalan and prednisone. Among these
patients, 93% were exposed for 6 months or longer and 19% were exposed for greater than one year.
Serious adverse reactions occurred in 39% of patients who received DARZALEX FASPRO. Serious adverse
reactions in >5% of patients included pneumonia and pyrexia. Fatal adverse reactions occurred in 3.0% of
patients.
DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) injection
Permanent discontinuation of DARZALEX FASPRO due to an adverse reaction occurred in 4.5% of patients.
The adverse reaction resulting in permanent discontinuation of DARZALEX FASPRO in more than 1 patient was
neutropenic sepsis.
Dosage interruptions (defined as dose delays or skipped doses) due to an adverse reaction occurred in
51% of patients who received DARZALEX FASPRO. Adverse reactions requiring dosage interruptions in
>5% of patients included thrombocytopenia, neutropenia, anemia, and pneumonia.
The most common adverse reactions (≥20%) were upper respiratory tract infection, constipation, nausea,
fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain.
Table 1 summarizes the adverse reactions in patients who received DARZALEX FASPRO with bortezomib,
melphalan and prednisone (D-VMP) in PLEIADES.
Table 1: Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO with Bortezomib,
Melphalan and Prednisone (D-VMP) in PLEIADES
DARZALEX FASPRO
with Bortezomib, Melphalan
and Prednisone
(N=67)
Adverse Reaction
All Grades (%) Grades ≥3 (%)
Infections
Upper respiratory tract infection a 39 0
Bronchitis 16 0
Pneumonia b 15 7 #
Gastrointestinal disorders
Constipation 37 0
Nausea 36 0
Diarrhea 33 3 #
Vomiting 21 0
Abdominal pain c 13 0
General disorders and administration site conditions
Fatigue d 36 3
Pyrexia 34 0
Edema peripheral e 13 1#
Nervous system disorders
Peripheral sensory neuropathy 34 1#
Dizziness 10 0
Respiratory, thoracic and mediastinal disorders
Cough f 24 0
Psychiatric disorders
Insomnia 22 3 #
Musculoskeletal and connective tissue disorders
Back pain 21 3 #
Musculoskeletal chest pain 12 0
Metabolism and nutrition disorders
Decreased appetite 15 1 #
Skin and subcutaneous tissue disorders
Rash 13 0
Pruritus 12 0
Vascular disorders
Hypertension 13 6 #
Hypotension 10 3 #
a Upper respiratory tract infection includes nasopharyngitis, respiratory syncytial virus infection,
respiratory tract infection, rhinitis, tonsillitis, upper respiratory tract infection, and viral pharyngitis.
b Pneumonia includes lower respiratory tract infection, lung infection, pneumocystis jirovecii pneumonia,
pneumonia, and pneumonia bacterial.
c Abdominal pain includes abdominal pain, and abdominal pain upper.
d Fatigue includes asthenia, and fatigue.
e Edema peripheral includes edema, edema peripheral, and peripheral swelling.
f Cough includes cough, and productive cough.
# Only grade 3 adverse reactions occurred.
Clinically relevant adverse reactions in <10% of patients who received DARZALEX FASPRO with bortezomib,
melphalan and prednisone (D-VMP) include:
• General disorders and administration site conditions: infusion reaction, injection site reaction, chills
• Infections: herpes zoster, urinary tract infection, influenza, sepsis
• Musculoskeletal and connective tissue disorders: arthralgia, muscle spasms
• Nervous system disorders: headache, paresthesia
• Metabolism and nutrition disorders: hypocalcemia, hyperglycemia
• Respiratory, thoracic and mediastinal disorders: dyspnea, pulmonary edema
• Cardiac disorders: atrial fibrillation
Table 2 summarizes the laboratory abnormalities in patients who received DARZALEX FASPRO with
bortezomib, melphalan and prednisone (D-VMP) in PLEIADES.
Table 2: Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Who
Received DARZALEX FASPRO with Bortezomib, Melphalan and Prednisone (D-VMP) in
PLEIADES
DARZALEX FASPRO with Bortezomib, Melphalan and Prednisone a
Laboratory Abnormality
All Grades (%) Grades 3-4 (%)
Decreased leukocytes 96 52
Decreased lymphocytes 93 84
Decreased platelets 93 42
Decreased neutrophils 88 49
Decreased hemoglobin 48 19
a Denominator is based on the safety population treated with D-VMP (N=67).
Relapsed/Refractory Multiple Myeloma
In Combination with Lenalidomide and Dexamethasone
The safety of DARZALEX FASPRO with lenalidomide and dexamethasone (D-Rd) was evaluated in a singlearm
cohort of PLEIADES [see Clinical Studies (14.2) in Full Prescribing Information]. Patients received
DARZALEX FASPRO 1,800 mg/30,000 units administered subcutaneously once weekly from weeks 1 to
8, once every 2 weeks from weeks 9 to 24 and once every 4 weeks starting with week 25 until disease
progression or unacceptable toxicity (N=65) in combination with lenalidomide and dexamethasone. Among
these patients, 92% were exposed for 6 months or longer and 20% were exposed for greater than one year.
Serious adverse reactions occurred in 48% of patients who received DARZALEX FASPRO. Serious adverse
reactions in >5% of patients included pneumonia, influenza and diarrhea. Fatal adverse reactions occurred
in 3.1% of patients.