DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) injection
Permanent discontinuation of DARZALEX FASPRO due to an adverse reaction occurred in 11% of patients
who received DARZALEX FASPRO. Adverse reactions resulting in permanent discontinuation of DARZALEX
FASPRO in more than 1 patient were pneumonia and anemia.
Dosage interruptions due to an adverse reaction occurred in 63% of patients who received DARZALEX
FASPRO. Adverse reactions requiring dosage interruptions in >5% of patients included neutropenia,
pneumonia, upper respiratory tract infection, influenza, dyspnea, and blood creatinine increased.
The most common adverse reactions (≥20%) were fatigue, diarrhea, upper respiratory tract infection,
muscle spasms, constipation, pyrexia, pneumonia, and dyspnea.
Table 3 summarizes the adverse reactions in patients who received DARZALEX FASPRO with lenalidomide
and dexamethasone (D-Rd) in PLEIADES.
Table 3: Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO with Lenalidomide and
Dexamethasone (D-Rd) in PLEIADES
DARZALEX FASPRO with Lenalidomide and
Dexamethasone
(N=65)
Adverse Reaction
All Grades (%) Grades ≥3 (%)
General disorders and administration site conditions
Fatigue a 52 5 #
Pyrexia 23 2 #
Edema peripheral 18 3 #
Gastrointestinal disorders
Diarrhea 45 5 #
Constipation 26 2 #
Nausea 12 0
Vomiting 11 0
Infections
Upper respiratory tract infection b 43 3 #
Pneumonia c 23 17
Bronchitis d 14 2 #
Urinary tract infection 11 0
Musculoskeletal and connective tissue disorders
Muscle spasms 31 2 #
Back pain 14 0
Respiratory, thoracic and mediastinal disorders
Dyspnea e 22 3
Cough f 14 0
Nervous system disorders
Peripheral sensory neuropathy 17 2 #
Psychiatric disorders
Insomnia 17 5 #
Metabolism and nutrition disorders
Hyperglycemia 12 9 #
Hypocalcemia 11 0
a Fatigue includes asthenia, and fatigue.
b Upper respiratory tract infection includes nasopharyngitis, pharyngitis, respiratory tract infection viral,
rhinitis, sinusitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.
c Pneumonia includes lower respiratory tract infection, lung infection, and pneumonia.
d Bronchitis includes bronchitis, and bronchitis viral.
e Dyspnea includes dyspnea, and dyspnea exertional.
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
lenalidomide and dexamethasone (D-Rd) include:
• Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal chest pain
• Nervous system disorders: dizziness, headache, paresthesia
• Skin and subcutaneous tissue disorders: rash, pruritus
• Gastrointestinal disorders: abdominal pain
• Infections: influenza, sepsis, herpes zoster
• Metabolism and nutrition disorders: decreased appetite
• Cardiac disorders: atrial fibrillation
• General disorders and administration site conditions: chills, infusion reaction, injection site reaction
• Vascular disorders: hypotension, hypertension
Table 4 summarizes the laboratory abnormalities in patients who received DARZALEX FASPRO with
lenalidomide and dexamethasone (D-Rd) in PLEIADES.
Table 4: Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Who
Received DARZALEX FASPRO with Lenalidomide and Dexamethasone (D-Rd) in PLEIADES
DARZALEX FASPRO with Lenalidomide and Dexamethasone a
Laboratory Abnormality
All Grades (%) Grades 3-4 (%)
Decreased leukocytes 94 34
Decreased lymphocytes 82 58
Decreased platelets 86 9
Decreased neutrophils 89 52
Decreased hemoglobin 45 8
a Denominator is based on the safety population treated with D-Rd (N=65).
Monotherapy
The safety of DARZALEX FASPRO as monotherapy was evaluated in COLUMBA [see Clinical Trials (14.2)
in Full Prescribing Information]. Patients received DARZALEX FASPRO 1,800 mg/30,000 units administered
subcutaneously or daratumumab 16 mg/kg administered intravenously; each administered 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. Among patients receiving DARZALEX FASPRO, 37%
were exposed for 6 months or longer and 1% were exposed for greater than one year.
Serious adverse reactions occurred in 26% of patients who received DARZALEX FASPRO. Fatal adverse
reactions occurred in 5% of patients. Fatal adverse reactions occurring in more than 1 patient were general
physical health deterioration, septic shock, and respiratory failure.
Permanent discontinuation due to an adverse reaction occurred in 10% of patients who received DARZALEX
FASPRO. Adverse reactions resulting in permanent discontinuation of DARZALEX FASPRO in more than 2
patients were thrombocytopenia and hypercalcemia.
Dosage interruptions due to an adverse reaction occurred in 26% of patients who received DARZALEX
FASPRO. Adverse reactions requiring dosage interruption in >5% of patients included thrombocytopenia.
The most common adverse reaction (≥20%) was upper respiratory tract infection.
Table 5 summarizes the adverse reactions in COLUMBA.
DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) injection
Table 5: Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO or Intravenous
Daratumumab in COLUMBA
DARZALEX FASPRO
(N=260)
Intravenous Daratumumab
(N=258)
Adverse Reaction
All Grades
(%)
Grade ≥3
(%)
All Grades
(%)
Grade ≥3
(%)
Infections
Upper respiratory tract infection a 24 1 # 22 1 #
Pneumonia b 8 5 10 6 @
Gastrointestinal disorders
Diarrhea 15 1 # 11 0.4 #
Nausea 8 0.4 # 11 0.4 #
General disorders and administration site conditions
Fatigue c 15 1 # 16 2 #
Infusion reactions d 13 2 # 34 5 #
Pyrexia 13 0 13 1 #
Chills 6 0.4 # 12 1 #
Musculoskeletal and connective tissue disorders
Back pain 10 2 # 12 3 #
Respiratory, thoracic and mediastinal disorders
Cough e 9 1 # 14 0
Dyspnea f 6 1 # 11 1 #
a Upper respiratory tract infection includes acute sinusitis, nasopharyngitis, pharyngitis, respiratory syncytial
virus infection, respiratory tract infection, rhinitis, rhinovirus infection, sinusitis, and upper respiratory tract
infection.
b Pneumonia includes lower respiratory tract infection, lung infection, pneumocystis jirovecii pneumonia,
and pneumonia.
c Fatigue includes asthenia, and fatigue.
d Infusion reactions includes terms determined by investigators to be related to infusion.
e Cough includes cough, and productive cough.
f Dyspnea includes dyspnea, and dyspnea exertional.
# Only grade 3 adverse reactions occurred.
@ Grade 5 adverse reactions occurred.
Clinically relevant adverse reactions in <10% of patients who received DARZALEX FASPRO include:
• General disorders and administration site conditions: injection site reaction, peripheral edema
• Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal chest pain, muscle
spasms
• Gastrointestinal disorders: constipation, vomiting, abdominal pain,
• Metabolism and nutrition disorders: decreased appetite, hyperglycemia, hypocalcemia, dehydration
• Psychiatric disorders: insomnia
• Vascular disorders: hypertension, hypotension
• Nervous system disorders: dizziness, peripheral sensory neuropathy, paresthesia
• Infections: bronchitis, influenza, urinary tract infection, herpes zoster, sepsis, hepatitis B reactivation
• Skin and subcutaneous tissue disorders: pruritus, rash
• Cardiac disorders: atrial fibrillation
• Respiratory, thoracic and mediastinal disorders: pulmonary edema
Table 6 summarizes the laboratory abnormalities in COLUMBA.
Table 6: Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Receiving
DARZALEX FASPRO or Intravenous Daratumumab in COLUMBA
DARZALEX
Intravenous Daratumumab a
FASPRO a
Laboratory Abnormality
All Grades
(%)
Grades 3-4
(%)
All Grades
(%)
Grades 3-4
(%)
Decreased leukocytes 65 19 57 14
Decreased lymphocytes 59 36 56 36
Decreased neutrophils 55 19 43 11
Decreased platelets 43 16 45 14
Decreased hemoglobin 42 14 39 16
a Denominator is based on the safety population treated with DARZALEX FASPRO (N=260) and Intravenous
Daratumumab (N=258).
Immunogenicity
As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody formation
is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of
antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including
assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying
disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the
incidence of antibodies in other studies or to other daratumumab products or other hyaluronidase products
may be misleading.
Treatment-emergent anti-daratumumab antibodies were tested in 451 patients treated with DARZALEX FASPRO
as monotherapy or as part of a combination therapy. One patient (0.2%) who received DARZALEX FASPRO as
monotherapy tested positive for anti-daratumumab antibodies and transient neutralizing antibodies. However,
the incidence of antibody development might not have been reliably determined because the assays that
were used have limitations in detecting anti-daratumumab antibodies in the presence of high concentrations
of daratumumab.
Treatment-emergent anti-rHuPH20 antibodies developed in 8% (19/255) of patients who received DARZALEX
FASPRO as monotherapy and in 8% (16/192) of patients who received DARZALEX FASPRO as part of a
combination therapy. The anti-rHuPH20 antibodies did not appear to affect daratumumab exposures. None
of the patients who tested positive for anti-rHuPH20 antibodies tested positive for neutralizing antibodies.
Postmarketing Experience
The following adverse reactions have been identified with use of intravenous daratumumab. Because these
reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably
estimate their frequency or establish a causal relationship to drug exposure.
Immune System: Anaphylactic reaction
Gastrointestinal: Pancreatitis
DRUG INTERACTIONS
Effects of Daratumumab on Laboratory Tests
Interference with Indirect Antiglobulin Tests (Indirect Coombs Test)
Daratumumab binds to CD38 on RBCs and interferes with compatibility testing, including antibody screening and
cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol
(DTT) to disrupt daratumumab binding [see References] or genotyping. Since the Kell blood group system is
also sensitive to DTT treatment, supply K-negative units after ruling out or identifying alloantibodies using
DTT-treated RBCs.