Darzalex

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 4/22/2022
Darzalex Side Effects Center

What Is Darzalex?

Darzalex (daratumumab) injection is a human CD38-directed monoclonal antibody indicated for the treatment of patients with multiple myeloma 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.

What Are Side Effects of Darzalex?

Common side effects of Darzalex include:

Dosage for Darzalex

The recommended dose of Darzalex is 16 mg/kg body weight and dosing follows a set schedule. Patients are pre-medicated with corticosteroids, antipyretics, and antihistamines.

What Drugs, Substances, or Supplements Interact with Darzalex?

Darzalex may interact with other drugs. Tell your doctor all medications and supplements you use.

Darzalex During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant, plan to become pregnant, or become pregnant while taking Darzalex. It is unknown if Darzalex passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Darzalex (daratumumab) injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Darzalex Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, itchy, nauseated, or if you have a headache, stuffy nose, runny nose, cough, fever, chills, wheezing, trouble breathing, or a tight feeling in your throat.

Call your doctor at once if you have:

  • cough with yellow or green mucus;
  • stabbing chest pain, wheezing, feeling short of breath;
  • numbness, tingling, burning pain; or
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • nausea, constipation, diarrhea;
  • fever;
  • shortness of breath;
  • nerve problems causing tingling, numbness, or pain;
  • feeling tired or weak;
  • swelling in your hands, ankles, or feet; or
  • cold symptoms such as stuffy nose, sneezing, cough, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Darzalex (Daratumumab Intravenous Injection)

Darzalex Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Infusion-related reactions [see WARNINGS AND PRECAUTIONS].
  • Neutropenia [see WARNINGS AND PRECAUTIONS].
  • Thrombocytopenia [see WARNINGS 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.

The safety data described below reflects exposure to DARZALEX (16 mg/kg) in 2,459 patients with multiple myeloma including 2,303 patients who received DARZALEX in combination with background regimens and 156 patients who received DARZALEX as monotherapy. In this pooled safety population, the most common adverse reactions (≥20%) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia.

Newly Diagnosed Multiple Myeloma Ineligible For Autologous Stem Cell Transplant

Combination Treatment With Lenalidomide And Dexamethasone (DRd)

The safety of DARZALEX in combination with lenalidomide and dexamethasone was evaluated in MAIA [see Clinical Studies]. Adverse reactions described in Table 7 reflect exposure to DARZALEX for a median treatment duration of 25.3 months (range: 0.1 to 40.44 months) for daratumumab-lenalidomide-dexamethasone (DRd) and of 21.3 months (range: 0.03 to 40.64 months) for lenalidomide-dexamethasone (Rd).

Serious adverse reactions with a 2% greater incidence in the DRd arm compared to the Rd arm were pneumonia (DRd 15% vs Rd 8%), bronchitis (DRd 4% vs Rd 2%) and dehydration (DRd 2% vs Rd <1%).

Table 7: Adverse Reactions Reported in ≥10% of Patients and With at Least a 5% Greater Frequency in the DRd Arm in MAIA

Body System
Adverse Reaction
DRd
(N=364)
Rd
(N=365)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Gastrointestinal disorders
Diarrhea 57 7 0 46 4 0
Constipation 41 1 <1 36 <1 0
Nausea 32 1 0 23 1 0
Vomiting 17 1 0 12 <1 0
Infections
Upper respiratory tract infectiona 52 2 <1 36 2 <1
Bronchitisb 29 3 0 21 1 0
Pneumoniac 26 14 1 14 7 1
Urinary tract infection 18 2 0 10 2 0
General disorders and administration site conditions
Infusion-related reactionsd 41 2 <1 0 0 0
Peripheral edemae 41 2 0 33 1 0
Fatigue 40 8 0 28 4 0
Asthenia 32 4 0 25 3 <1
Pyrexia 23 2 0 18 2 0
Chills 13 0 0 2 0 0
Musculoskeletal and connective tissue disorders
Back pain 34 3 <1 26 3 <1
Muscle spasms 29 1 0 22 1 0
Respiratory, thoracic and mediastinal disorders
Dyspneaf 32 3 <1 20 1 0
Coughg 30 <1 0 18 0 0
Nervous system disorders
Peripheral sensory neuropathy 24 1 0 15 0 0
Headache 19 1 0 11 0 0
Paresthesia 16 0 0 8 0 0
Metabolism and nutrition disorders
Decreased appetite 22 1 0 15 <1 <1
Hyperglycemia 14 6 1 8 3 1
Hypocalcemia 14 1 <1 9 1 1
Vascular disorders
Hypertensionh 13 6 <1 7 4 0
Key: D=daratumumab, Rd=lenalidomide-dexamethasone.
aAcute sinusitis, Bacterial rhinitis, Laryngitis, Metapneumovirus infection, Nasopharyngitis, Oropharyngeal candidiasis, Pharyngitis, Respiratory syncytial virus infection, Respiratory tract infection, Respiratory tract infection viral, Rhinitis, Rhinovirus infection, Sinusitis, Tonsillitis, Tracheitis, Upper respiratory tract infection, Viral pharyngitis, Viral rhinitis, Viral upper respiratory tract infection
bBronchiolitis, Bronchitis, Bronchitis viral, Respiratory syncytial virus bronchiolitis, Tracheobronchitis
cAtypical pneumonia, Bronchopulmonary aspergillosis, Lung infection, Pneumocystis jirovecii infection, Pneumocystis jirovecii pneumonia, Pneumonia, Pneumonia aspiration, Pneumonia pneumococcal, Pneumonia viral, Pulmonary mycosis
dInfusion-related reaction includes terms determined by investigators to be related to infusion
eGeneralized edema, Gravitational edema, Edema, Peripheral edema, Peripheral swelling
fDyspnea, Dyspnea exertional
gCough, Productive cough
hBlood pressure increased, Hypertension

Laboratory abnormalities worsening during treatment from baseline listed in Table 8.

Table 8: Treatment-Emergent Hematology Laboratory Abnormalities in MAIA

DRd
(N=364)
Rd
(N=365)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Leukopenia 90 30 5 82 20 4
Neutropenia 91 39 17 77 28 11
Lymphopenia 84 41 11 75 36 6
Thrombocytopenia 67 6 3 58 7 4
Anemia 47 13 0 57 24 0
Key: D=daratumumab, Rd=lenalidomide-dexamethasone.

Combination Treatment With Bortezomib, Melphalan And Prednisone

The safety of DARZALEX in combination with bortezomib, melphalan and prednisone was evaluated in ALCYONE [see Clinical Studies]. Adverse reactions described in Table 9 reflect exposure to DARZALEX for a median treatment duration of 14.7 months (range: 0 to 25.8 months) for daratumumab, bortezomib, melphalan and prednisone (D-VMP) and of 12 months (range: 0.1 to 14.9 months) for VMP.

Serious adverse reactions with at least a 2% greater incidence in the D-VMP arm compared to the VMP arm were pneumonia (D-VMP 11% vs VMP 4%), upper respiratory tract infection (D­VMP 5% vs VMP 1%), and pulmonary edema (D-VMP 2% vs VMP 0%).

Table 9: Adverse Reactions Reported in ≥10% of Patients and With at Least a 5% Greater Frequency in the D-VMP Arm in ALCYONE

Body System
Adverse Reaction
D-VMP
(N=346)
VMP
(N=354)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Infections
Upper respiratory tract infectiona 48 5 0 28 3 0
Pneumoniab 16 12 < 1 6 5 < 1
General disorders and administration site conditions
Infusion-related reactionsc 28 4 1 0 0 0
Peripheral edemad 21 1 < 1 14 1 0
Respiratory, thoracic and mediastinal disorders
Coughe 16 < 1 0 8 < 1 0
Dyspneaf 13 2 1 5 1 0
Vascular disorders
Hypertensiong 10 4 <1 3 2 0
Key: D=daratumumab, VMP=bortezomib-melphalan-prednisone
a upper respiratory tract infection, bronchitis, bronchitis bacterial, epiglottitis, laryngitis, laryngitis bacterial, metapneumovirus infection, nasopharyngitis, oropharyngeal candidiasis, pharyngitis, pharyngitis streptococcal, respiratory syncytial virus infection, respiratory tract infection, respiratory tract infection viral, rhinitis, sinusitis, tonsillitis, tracheitis, tracheobronchitis, viral pharyngitis, viral rhinitis, viral upper respiratory tract infection
b pneumonia, lung infection, pneumonia aspiration, pneumonia bacterial, pneumonia pneumococcal, pneumonia streptococcal, pneumonia viral, and pulmonary sepsis
c Infusion-related reaction includes terms determined by investigators to be related to infusion
d edema peripheral, generalized edema, peripheral swelling
e cough, productive cough
f dyspnea, dyspnea exertional
g hypertension, blood pressure increased

Laboratory abnormalities worsening during treatment from baseline listed in Table 10.

Table 10: Treatment-Emergent Hematology Laboratory Abnormalities in ALCYONE

D-VMP
(N=346)
VMP
(N=354)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Thrombocytopenia 88 27 11 88 26 16
Neutropenia 86 34 10 87 32 11
Lymphopenia 85 46 12 83 44 9
Anemia 47 18 0 50 21 0
Key: D=daratumumab, VMP=bortezomib-melphalan-prednisone

Newly Diagnosed Multiple Myeloma Eligible For Autologous Stem Cell Transplant

Combination Treatment With Bortezomib, Thalidomide And Dexamethasone (DVTd)

The safety of DARZALEX in combination with bortezomib, thalidomide and dexamethasone was evaluated in CASSIOPEIA [see Clinical Studies]. Adverse reactions described in Table 11 reflect exposure to DARZALEX up to day 100 post-transplant. The median duration of induction/ASCT/consolidation treatment was 8.9 months (range: 7.0 to 12.0 months) for DVTd and 8.7 months (range: 6.4 to 11.5 months) for VTd.

Serious adverse reactions with a 2% greater incidence in the DVTd arm compared to the VTd arm were bronchitis (DVTd 2% vs VTd <1%) and pneumonia (DVTd 6% vs VTd 4%).

Table 11: Adverse Reactions Reported in ≥ 10% of Patients and With at Least a 5% Greater Frequency in the DVTd Arm in CASSIOPEIA

Body System
Adverse Reaction
DVTd
(N=536)
VTd
(N=538)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
General disorders and administration site conditions
Infusion-related reactions a 35 3 <1 0 0 0
Pyrexia 26 2 <1 21 2 0
Gastrointestinal disorders
Nausea 30 4 0 24 2 <1
Vomiting 16 2 0 10 2 0
Infections
Upper respiratory tract infectionb 27 1 0 17 1 0
Bronchitisc 20 1 0 13 1 0
Respiratory, thoracic and mediastinal disorders
Coughd 17 0 0 9 0 0
Vascular disorders
Hypertension 10 4 0 5 2 0
Key: D=daratumumab, VTd=bortezomib-thalidomide -dexamethasone.
a Infusion-related reaction includes terms determined by investigators to be related to infusion
b Laryngitis, Laryngitis viral, Metapneumovirus infection, Nasopharyngitis, Oropharyngeal candidiasis, Pharyngitis, Respiratory syncytial virus infection, Respiratory tract infection, Respiratory tract infection viral, Rhinitis, Rhinovirus infection, Sinusitis, Tonsillitis, Tracheitis, Upper respiratory tract infection, Viral pharyngitis, Viral rhinitis, Viral upper respiratory tract infection
c Bronchiolitis, Bronchitis, Bronchitis chronic, Respiratory syncytial virus bronchitis, Tracheobronchitis
d Cough, Productive cough
Note: Hematology laboratory related toxicities were excluded and reported separately in the table below

Table 12: Treatment-Emergent Hematology Laboratory Abnormalities in CASSIOPEIA

DVTd
(N=536)
VTd
(N=538)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Lymphopenia 95 44 15 91 37 10
Leukopenia 82 14 10 57 6 9
Thrombocytopenia 81 9 5 58 8 3
Neutropenia 63 19 14 41 10 9
Anemia 36 4 0 35 5 0
Key: D=daratumumab, VTd=bortezomib-thalidomide -dexamethasone.

Relapsed/Refractory Multiple Myeloma

Combination Treatment With Lenalidomide And Dexamethasone

The safety of DARZALEX in combination with lenalidomide and dexamethasone was evaluated in POLLUX [see Clinical Studies]. Adverse reactions described in Table 13 reflect exposure to DARZALEX for a median treatment duration of 13.1 months (range: 0 to 20.7 months) for daratumumab-lenalidomide-dexamethasone (DRd) and of 12.3 months (range: 0.2 to 20.1 months) for lenalidomide-dexamethasone (Rd).

Serious adverse reactions occurred in 49% of patients in the DRd arm compared with 42% in the Rd arm. Serious adverse reactions with at least a 2% greater incidence in the DRd arm compared to the Rd arm were pneumonia (DRd 12% vs Rd 10%), upper respiratory tract infection (DRd 7% vs Rd 4%), influenza and pyrexia (DRd 3% vs Rd 1% for each).

Adverse reactions resulted in discontinuations for 7% (n=19) of patients in the DRd arm versus 8% (n=22) in the Rd arm.

Table 13: Adverse Reactions Reported in ≥ 10% of Patients and With at Least a 5% Greater Frequency in the DRd Arm in POLLUX

Adverse Reaction DRd
(N=283)
Rd
(N=281)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Infections
Upper respiratory tract infectiona 65 6 < 1 51 4 0
General disorders and administration site conditions
Infusion-related reactionsb 48 5 0 0 0 0
Fatigue 35 6 < 1 28 2 0
Pyrexia 20 2 0 11 1 0
Gastrointestinal disorders
Diarrhea 43 5 0 25 3 0
Nausea 24 1 0 14 0 0
Vomiting 17 1 0 5 1 0
Respiratory, thoracic and mediastinal disorders
Coughc 30 0 0 15 0 0
Dyspnead 21 3 < 1 12 1 0
Musculoskeletal and connective tissue disorders
Muscle spasms 26 1 0 19 2 0
Nervous system disorders
Headache 13 0 0 7 0 0
Key: D=daratumumab, Rd=lenalidomide-dexamethasone.
a upper respiratory tract infection, bronchitis, sinusitis, respiratory tract infection viral, rhinitis, pharyngitis, respiratory tract infection, metapneumovirus infection, tracheobronchitis, viral upper respiratory tract infection, laryngitis, respiratory syncytial virus infection, staphylococcal pharyngitis, tonsillitis, viral pharyngitis, acute sinusitis, nasopharyngitis, bronchiolitis, bronchitis viral, pharyngitis streptococcal, tracheitis, upper respiratory tract infection bacterial, bronchitis bacterial, epiglottitis, laryngitis viral, oropharyngeal candidiasis, respiratory moniliasis, viral rhinitis, acute tonsillitis, rhinovirus infection
b Infusion-related reaction includes terms determined by investigators to be related to infusion
c cough, productive cough, allergic cough
d dyspnea, dyspnea exertional

Laboratory abnormalities worsening during treatment from baseline listed in Table 14.

Table 14: Treatment-Emergent Hematology Laboratory Abnormalities in POLLUX

DRd
(N=283)
Rd
(N=281)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Lymphopenia 95 42 10 87 32 6
Neutropenia 92 36 17 87 32 8
Thrombocytopenia 73 7 6 67 10 5
Anemia 52 13 0 57 19 0
Key: D=daratumumab, Rd=lenalidomide-dexamethasone.

Combination Treatment With Bortezomib And Dexamethasone

The safety of DARZALEX in combination with bortezomib and dexamethasone was evaluated in CASTOR [see Clinical Studies]. Adverse reactions described in Table 15 reflect exposure to DARZALEX for a median treatment duration of 6.5 months (range: 0 to 14.8 months) for daratumumab-bortezomib-dexamethasone (DVd) and of 5.2 months (range: 0.2 to 8.0 months) for bortezomib-dexamethasone (Vd) arm.

Serious adverse reactions occurred in 42% of patients in the DVd arm compared with 34% in the Vd arm. Serious adverse reactions with at least a 2% greater incidence in the DVd arm compared to the Vd arm were upper respiratory tract infection (DVd 5% vs Vd 2%), diarrhea and atrial fibrillation (DVd 2% vs Vd 0% for each).

Adverse reactions resulted in discontinuations for 7% (n=18) of patients in the DVd arm versus 9% (n=22) in the Vd arm.

Table 15: Adverse Reactions Reported in ≥10% of Patients and With at Least a 5% Greater Frequency in the DVd Arm CASTOR

Adverse Reaction DVd
(N=243)
Vd
(N=237)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Nervous system disorders
Peripheral sensory neuropathy 47 5 0 38 6 < 1
General disorders and administration site conditions
Infusion-related reactionsa 45 9 0 0 0 0
Peripheral edemab 22 1 0 13 0 0
Pyrexia 16 1 0 11 1 0
Infections
Upper respiratory tract infectionc 44 6 0 30 3 < 1
Gastrointestinal disorders
Diarrhea 32 3 < 1 22 1 0
Vomiting 11 0 0 4 0 0
Respiratory, thoracic and mediastinal disorders
Coughd 27 0 0 14 0 0
Dyspneae 21 4 0 11 1 0
Key: D=daratumumab, Vd=bortezomib-dexamethasone.
a Infusion-related reaction includes terms determined by investigators to be related to infusion
b edema peripheral, edema, generalized edema, peripheral swelling
c upper respiratory tract infection, bronchitis, sinusitis, respiratory tract infection viral, rhinitis, pharyngitis, respiratory tract infection, metapneumovirus infection, tracheobronchitis, viral upper respiratory tract infection, laryngitis, respiratory syncytial virus infection, staphylococcal pharyngitis, tonsillitis, viral pharyngitis, acute sinusitis, nasopharyngitis, bronchiolitis, bronchitis viral, pharyngitis streptococcal, tracheitis, upper respiratory tract infection bacterial, bronchitis bacterial, epiglottitis, laryngitis viral, oropharyngeal candidiasis, respiratory moniliasis, viral rhinitis, acute tonsillitis, rhinovirus infection
d cough, productive cough, allergic cough
e dyspnea, dyspnea exertional

Laboratory abnormalities worsening during treatment are listed in Table 16.

Table 16: Treatment-Emergent Hematology Laboratory Abnormalities in CASTOR

DVd
(N=243)
Vd
(N=237)
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Thrombocytopenia 90 28 19 85 22 13
Lymphopenia 89 41 7 81 24 3
Neutropenia 58 12 3 40 5 < 1
Anemia 48 13 0 56 14 0
Key: D=daratumumab, Vd=bortezomib-dexamethasone.

Combination Treatment With Twice-Weekly (20/56 mg/m²) Carfilzomib And Dexamethasone

The safety of DARZALEX in combination with twice weekly carfilzomib and dexamethasone was evaluated in CANDOR [see Clinical Studies]. Adverse reactions described in Table 17 reflect exposure to DARZALEX for a median treatment duration of 16.1 months (range: 0.1 to 23.7 months) for the daratumumab-carfilzomib-dexamethasone (DKd) group and median treatment duration of 9.3 months (range: 0.1 to 22.4 months) for the carfilzomib-dexamethasone group (Kd).

Serious adverse reactions occurred in 56% of patients who received DARZALEX in combination with Kd and 46% of patients who received Kd. The most frequent serious adverse reactions reported in the DKd arm as compared with the Kd arm were pneumonia (DKd 14% vs Kd 9%), pyrexia (DKd 4.2% vs Kd 2.0%), influenza (DKd 3.9% vs Kd 1.3%), sepsis (DKd 3.9% vs Kd 1.3%), anemia (DKd 2.3% vs Kd 0.7%), bronchitis (DKd 1.9% vs Kd 0%), and diarrhea (DKd 1.6% vs Kd 0%). Fatal adverse reactions within 30 days of the last dose of any study treatment occurred in 10% of 308 patients who received DARZALEX in combination with Kd versus 5% of 153 patients who received Kd. The most frequent fatal adverse reaction was infection (4.5% vs 2.6%).

Permanent discontinuation of DARZALEX due to an adverse reaction occurred in 9% of patients. Adverse reactions (>1%) which resulted in permanent discontinuation of DARZALEX included pneumonia.

Infusion-related reactions that occurred on the day of administration of any DARZALEX dose or on the next day occurred in 18% of patients and that occurred on the day of administration of the first DARZALEX dose or the next day occurred in 12%.

Table 17: Adverse Reactions (≥15%) in Patients Who Received DARZALEX in Combination with Carfilzomib and Dexamethasone (DKd) in CANDOR

Adverse Reaction DKd
(N=308)
Kd
(N=153)
All Grades(%) Grades 3 or 4(%) All Grades(%) Grades 3 or 4(%)
General Disorders and Administration Site Conditions
Infusion-related reactionsa 41 12 28 5
Fatigueb 32 11 28 8
Pyrexia 20 1.9 15 0.7
Infections
Respiratory tract infectionc 40g 7 29 3.3
Pneumonia 18g 13 12 9
Bronchitis 17 2.6 12 1.3
Blood and lymphatic system disorders
Thrombocytopeniad 37 25 30 16
Anemiae 33 17 31 14
Gastrointestinal disorders
Diarrhea 32 3.9 14 0.7
Nausea 18 0 13 0.7
Vascular Disorders
Hypertension 31 18 28 13
Respiratory, Thoracic and Mediastinal Disorders
Coughf 21 0 21 0
Dyspnea 20 3.9 22 2.6
Psychiatric disorders
Insomnia 18 3.9 11 2
Musculoskeletal and connective tissue disorders
Back pain 16 1.9 10 1.3
Key: D=daratumumab; Kd=carfilzomib-dexamethasone
a The incidence of infusion related reactions is based on a group of symptoms (including hypertension, pyrexia, rash, myalgia, hypotension, blood pressure increased, urticaria, acute kidney injury, bronchospasm, face edema, hypersensitivity, rash, syncope, wheezing, eye pruritus, eyelid edema, renal failure, swelling face) related to infusion reactions which occurred within 1 day after DKd or Kd administration.
b Fatigue includes fatigue and asthenia.
c Respiratory tract infection includes respiratory tract infection, lower respiratory tract infection, upper respiratory tract infection and viral upper respiratory tract infection.
d Thrombocytopenia includes platelet count decreased and thrombocytopenia.
e Anemia includes anemia, hematocrit decreased and hemoglobin decreased.
f Cough includes productive cough and cough.
g Includes fatal adverse reactions.

Adverse Reactions Occurring At A Frequency Of < 15%
  • Blood and lymphatic system disorders: neutropenia, lymphopenia, leukopenia, febrile neutropenia
  • Cardiac disorders: atrial fibrillation
  • Gastrointestinal disorders: vomiting, constipation
  • General disorders and administration site conditions: peripheral edema, asthenia, chills
  • Infections: influenza, urinary tract infection, sepsis, septic shock
  • Metabolism and nutrition disorders: decreased appetite, hyperglycemia, hypocalcemia, dehydration
  • Musculoskeletal and connective tissue disorders: muscle spasms, arthralgia, musculoskeletal chest pain
  • Nervous system disorders: headache, dizziness, peripheral sensory neuropathy, paresthesia, posterior reversible encephalopathy syndrome
  • Respiratory, thoracic and mediastinal disorders: pulmonary edema
  • Skin and subcutaneous tissue disorders: rash, pruritus
Combination Treatment With Once-Weekly (20/70 mg/m²) Carfilzomib And Dexamethasone

The safety of DARZALEX in combination with once-weekly carfilzomib and dexamethasone was evaluated in EQUULEUS [see Clinical Studies]. Adverse reactions described in Table 18 reflect exposure to DARZALEX for a median treatment duration of 19.8 months (range: 0.3 to 34.5 months).

Serious adverse reactions were reported in 48% of patients. The most frequent serious adverse reactions reported were pneumonia (4.7%), upper respiratory tract infection (4.7%), basal cell carcinoma (4.7%), influenza (3.5%), general physical health deterioration (3.5%), and hypercalcemia (3.5%). Fatal adverse reactions within 30 days of the last dose of any study treatment occurred in 3.5% of patients who died of general physical health deterioration, multi-organ failure secondary to pulmonary aspergillosis, and disease progression.

Permanent discontinuation of DARZALEX due to an adverse reaction occurred in 8% of patients. No adverse reactions which resulted in permanent discontinuation of DARZALEX occurred in more than one patient.

Infusion-related reactions that occurred on the day of administration of any DARZALEX dose or on the next day occurred in 44% of patients. For patients who received the split first dose of DARZALEX, infusion-related reactions that occurred in 36% and 4% on the first and second day of administration of DARZALEX, respectively.

Table 18: Adverse Reactions (≥15%) of Patients Who Received DARZALEX in Combination with Carfilzomib and Dexamethasone in EQUULEUS

Adverse Reaction DKd
(N=85)
All Grades (%) Grades 3 or 4 (%)
Blood and lymphatic system disorders
Thrombocytopeniaa 68 32
Anemiab 52 21
Neutropeniac 31 21
Lymphopeniad 29 25
General disorder and administration site conditions
Fatiguee 54 18
Infusion-related reactionsf 53 12
Pyrexia 37 1.2
Infections
Respiratory tract infectiong 53 3.5
Bronchitis 19 0
Nasopharyngitis 18 0
Influenza 17 3.5
Gastrointestinal disorders
Nausea 42 1.2
Vomiting 40 1.2
Diarrhea 38 2.4
Constipation 17 0
Respiratory, thoracic and mediastinal disorders
Dyspnea 35 3.5
Coughh 33 0
Vascular disorders
Hypertension 33 20
Psychiatric disorders
Insomnia 33 4.7
Nervous system disorders
Headache 27 1.2
Musculoskeletal and connective tissue disorders
Back pain 25 0
Pain in extremity 15 0
Key: D=daratumumab; Kd=carfilzomib-dexamethasone
a Thrombocytopenia includes platelet count decreased and thrombocytopenia.
b Anemia includes anemia, hematocrit decreased and hemoglobin decreased.
c Neutropenia includes neutrophil count decreased and neutropenia.
d Lymphopenia includes lymphocyte count decreased and lymphopenia
e Fatigue includes fatigue and asthenia.
f The incidence of infusion related reactions is based on a group of symptoms (including hypertension, pyrexia, rash, myalgia, hypotension, blood pressure increased, urticaria, acute kidney injury, bronchospasm, face edema, hypersensitivity, rash, syncope, wheezing, eye pruritus, eyelid edema, renal failure, swelling face) related to infusion reactions which occurred within 1 day after DKd administration.
g Respiratory tract infection includes respiratory tract infection, lower respiratory tract infection, upper respiratory tract infection and viral upper respiratory tract infection.
h Cough includes productive cough and cough.

Adverse Reactions Occurring At A Frequency Of < 15%
  • Blood and lymphatic system disorders: leukopenia, febrile neutropenia
  • Cardiac disorders: atrial fibrillation
  • Gastrointestinal disorders: pancreatitis
  • General disorders and administration site conditions: peripheral edema, chills
  • Infections: pneumonia, urinary tract infection, sepsis, septic shock
  • Metabolism and nutrition disorders: decreased appetite, hyperglycemia, dehydration, hypocalcemia
  • Musculoskeletal and connective tissue disorders: muscle spasms, musculoskeletal chest pain, arthralgia
  • Nervous system disorders: dizziness, paresthesia, peripheral sensory neuropathy
  • Skin and subcutaneous tissue disorders: pruritus, rash
Combination Treatment With Pomalidomide And Dexamethasone

The safety of DARZALEX in combination with pomalidomide and dexamethasone was evaluated in EQUULEUS [see Clinical Studies]. Adverse reactions described in Table 19 reflect exposure to DARZALEX, pomalidomide and dexamethasone (DPd) for a median treatment duration of 6 months (range: 0.03 to 16.9 months).

The overall incidence of serious adverse reactions was 49%. Serious adverse reactions reported in ≥5% patients included pneumonia (7%). Adverse reactions resulted in discontinuations for 13% of patients.

Table 19: Adverse Reactions With Incidence ≥10% Reported in EQUULEUS

Adverse Reaction DPd
(N=103)
All Grades (%) Grade 3 (%) Grade 4 (%)
General disorders and administration site conditions
Fatigue 50 10 0
Infusion-related reactionsa 50 4 0
Pyrexia 25 1 0
Chills 20 0 0
Edema peripheralb 17 4 0
Asthenia 15 0 0
Non-cardiac chest pain 15 0 0
Pain 11 0 0
Infections
Upper respiratory tract infectionc 50 4 1
Pneumoniad 15 8 2
Respiratory, thoracic and mediastinal disorders
Coughe 43 1 0
Dyspneaf 33 6 1
Nasal congestion 16 0 0
Gastrointestinal disorders
Diarrhea 38 3 0
Constipation 33 0 0
Nausea 30 0 0
Vomiting 21 2 0
Musculoskeletal and connective tissue disorders
Muscle spasms 26 1 0
Back pain 25 6 0
Arthralgia 22 2 0
Pain in extremity 15 0 0
Bone pain 13 4 0
Musculoskeletal chest pain 13 2 0
Psychiatric disorders
Insomnia 23 2 0
Anxiety 13 0 0
Nervous system disorders
Dizziness 21 2 0
Tremor 19 3 0
Headache 17 0 0
Metabolism and nutrition disorders
Hypokalemia 16 3 0
Hyperglycemia 13 5 1
Decreased appetite 11 0 0
Key: D=daratumumab, Pd=pomalidomide-dexamethasone.
a Infusion-related reaction includes terms determined by investigators to be related to infusion
b edema, edema peripheral, peripheral swelling.
c acute tonsillitis, bronchitis, laryngitis, nasopharyngitis, pharyngitis, respiratory syncytial virus infection, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection
d lung infection, pneumonia, pneumonia aspiration
e cough, productive cough, allergic cough f dyspnea, dyspnea exertional

Laboratory abnormalities worsening during treatment are listed in Table 20.

Table 20: Treatment-Emergent Hematology Laboratory Abnormalities in EQUULEUS

DPd
(N=103)
All Grades (%) Grade 3 (%) Grade 4 (%)
Neutropenia 95 36 46
Lymphopenia 94 45 26
Thrombocytopenia 75 10 10
Anemia 57 30 0
Key: D=daratumumab, Pd=pomalidomide-dexamethasone.

Monotherapy

The safety of DARZALEX was evaluated in 156 adult patients with relapsed and refractory multiple myeloma in three open-label, clinical trials. Patients received DARZALEX 16 mg/kg. The median duration of exposure was 3.3 months (range: 0.03 to 20.04 months).

Serious adverse reactions were reported in 51 (33%) patients. The most frequent serious adverse reactions were pneumonia (6%), general physical health deterioration (3%), and pyrexia (3%).

Adverse reactions resulted in treatment delay for 24 (15%) patients, most frequently for infections. Adverse reactions resulted in discontinuations for 6 (4%) patients.

Adverse reactions occurring in at least 10% of patients are presented in Table 21. Table 22 describes Grade 3-4 laboratory abnormalities reported at a rate of ≥10%.

Table 21: Adverse Reactions With Incidence ≥10% in Patients With Multiple Myeloma Treated With DARZALEX 16 mg/kg

Adverse Reaction DARZALEX
(N=156)
All Grades (%) Grade 3 (%) Grade 4 (%)
General disorders and administration site conditions
Infusion-related reactiona 48 3 0
Fatigue 39 2 0
Pyrexia 21 1 0
Chills 10 0 0
Gastrointestinal disorders
Nausea 27 0 0
Diarrhea 16 1 0
Constipation 15 0 0
Vomiting 14 0 0
Musculoskeletal and connective tissue disorders
Back pain 23 2 0
Arthralgia 17 0 0
Pain in extremity 15 1 0
Musculoskeletal chest pain 12 1 0
Respiratory, thoracic and mediastinal disorders
Cough 21 0 0
Nasal congestion 17 0 0
Dyspnea 15 1 0
Infections
Upper respiratory tract infection 20 1 0
Nasopharyngitis 15 0 0
Pneumoniab 11 6 0
Metabolism and nutrition disorders
Decreased appetite 15 1 0
Nervous system disorders
Headache 12 1 0
Vascular disorders
Hypertension 10 5 0
a Infusion-related reaction includes terms determined by investigators to be related to infusion
b Pneumonia also includes the terms streptococcal pneumonia and lobar pneumonia.

Table 22: Treatment-Emergent Grade 3-4 Laboratory Abnormalities (≥10%)

Daratumumab 16 mg/kg
(N=156)
All Grades (%) Grade 3 (%) Grade 4 (%)
Lymphopenia 72 30 10
Neutropenia 60 17 3
Thrombocytopenia 48 10 8
Anemia 45 19 0

Herpes Zoster Virus Reactivation

Prophylaxis for Herpes Zoster Virus reactivation was recommended for patients in some clinical trials of DARZALEX. In monotherapy studies, herpes zoster was reported in 3% of patients. In the combination therapy studies, herpes zoster was reported in 2-5% of patients receiving DARZALEX.

Infections

Grade 3 or 4 infections were reported as follows:

  • Relapsed/refractory patient studies: DVd: 21% vs. Vd: 19%; DRd: 28% vs. Rd: 23%; DPd: 28%; DKda: 37%, Kda: 29%; DKdb:21%
  1. where carfilzomib 20/56 mg/m² was administered twice-weekly
  2. where carfilzomib 20/70 mg/m² was administered once-weekly
  • Newly diagnosed patient studies: D-VMP: 23%, VMP: 15%; DRd: 32%, Rd: 23%; DVTd: 22%; VTd: 20%.

Pneumonia was the most commonly reported severe (Grade 3 or 4) infection across studies. In active controlled studies, discontinuations from treatment due to infections occurred in 1-4% of patients.

Fatal infections (Grade 5) were reported as follows:

  • Relapsed/refractory patient studies: DVd: 1%, Vd: 2%; DRd: 2%, Rd: 1%; DPd: 2%; DKda: 5%, Kda: 3%; DKdb: 0%
  1. where carfilzomib 20/56 mg/m² was administered twice-weekly
  2. where carfilzomib 20/70 mg/m² was administered once-weekly
  • Newly diagnosed patient studies: D-VMP: 1%, VMP: 1%; DRd: 2%, Rd: 2%; DVTd: 0%, VTd: 0%.

Fatal infections were generally infrequent and balanced between the DARZALEX containing regimens and active control arms. Fatal infections were primarily due to pneumonia and sepsis.

Hepatitis B Virus (HBV) Reactivation

Hepatitis B virus reactivation has been reported in less than 1% of patients (including fatal cases) treated with DARZALEX in clinical trials.

Other Clinical Trials Experience

The following adverse reactions have been reported following administration of daratumumab and hyaluronidase for subcutaneous injection:

Nervous System disorders: Syncope

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 may be misleading.

In clinical trials of patients with multiple myeloma treated with DARZALEX as monotherapy or as combination therapies, none of the 111 evaluable monotherapy patients, and 2 of the 1,383 evaluable combination therapy patients, tested positive for anti-daratumumab antibodies. One patient administered DARZALEX as combination therapy, developed transient neutralizing antibodies against daratumumab. However, this assay has limitations in detecting anti­daratumumab antibodies in the presence of high concentrations of daratumumab; therefore, the incidence of antibody development might not have been reliably determined.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of 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 disorders: Anaphylactic reaction, IRR (including deaths)

Gastrointestinal disorders: Pancreatitis Infections: Cytomegalovirus, Listeriosis

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.

If an emergency transfusion is required, administer non-cross-matched ABO/RhD-compatible RBCs per local blood bank practices.

Interference With Serum Protein Electrophoresis And Immunofixation Tests

Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). False positive SPE and IFE assay results may occur for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, where daratumumab interference is suspected, consider using a FDA-approved daratumumab-specific IFE assay to distinguish daratumumab from any remaining endogenous M protein in the patient's serum, to facilitate determination of a complete response.

Read the entire FDA prescribing information for Darzalex (Daratumumab Intravenous Injection)

© Darzalex Patient Information is supplied by Cerner Multum, Inc. and Darzalex Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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