Does Darzalex (daratumumab) cause side effects?

Darzalex (daratumumab) is monoclonal antibody used to treat multiple myeloma

  • in combination with the medicines bortezomib, melphalan and prednisone, in people with newly diagnosed with multiple myeloma who cannot receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant);
  • in combination with the medicines lenalidomide and dexamethasone, or bortezomib and dexamethasone, in people who have received at least one prior medicine to treat multiple myeloma;
  • in combination with the medicines pomalidomide and dexamethasone in people who have received at least two prior medicines to treat multiple myeloma, including lenalidomide and a proteasome inhibitor; and
  • alone in people who have received at least three prior medicines to treat multiple myeloma, including a proteasome inhibitor and an immunomodulatory agent, or did not respond to a proteasome inhibitor and an immunomodulatory agent.

Common side effects of Darzalex include

Serious side effects of Darzalex include

Drug interactions of Darzalex include interference with compatibility testing, including antibody screening and cross-matching.

  • Darzalex may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. 

Darzalex may harm a fetus. Females who are able to become pregnant should use an effective method of birth control during treatment and for at least 3 months after your final dose of Darzalex. 

It is unknown if Darzalex passes into breast milk. Consult your doctor before breastfeeding

What are the important side effects of Darzalex (daratumumab)?

It is not known if Darzalex is safe and effective in children.

Before you receive Darzalex, tell your healthcare provider about all of your medical conditions, including if you:

Darzalex may cause serious reactions, including:

  • Infusion reactions. Infusion reactions are common with Darzalex and can be severe. Your healthcare provider may temporarily stop your infusion or completely stop treatment with Darzalex if you have infusion reactions. Get medical help right away if you get any of the following symptoms:
  • Changes in blood tests. Darzalex can affect the results of blood tests to match your blood type. These changes can last for up to 6 months after your final dose of Darzalex. Your healthcare provider will do blood tests to match your blood type before you start treatment with Darzalex. Tell all of your healthcare providers that you are being treated with Darzalex before receiving blood transfusions.
  • Decreases in blood cell counts. Darzalex can decrease white blood cell counts which help fight infections and blood cells called platelets which help to clot blood. Your healthcare provider will check your blood cell counts during treatment with Darzalex. Tell your healthcare provider if you develop fever or have signs of bruising or bleeding.
The most common side effects of Darzalex include:

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Darzalex. Call your doctor for medical advice about side effects.

Darzalex (daratumumab) side effects list for healthcare professionals

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

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 2,066 patients with multiple myeloma including 1,910 patients who received Darzalex in combination with background regimens and 156 patients who received Darzalex as monotherapy.

Newly Diagnosed Multiple Myeloma Ineligible For Autologous Stem Cell Transplant

Combination Treatment with Lenalidomide and Dexamethasone (DRd)

Adverse reactions described in the table below reflect exposure to Darzalex for a median treatment duration of 25.3 months (range: 0.1 to 40.44 months) for the daratumumablenalidomide-dexamethasone (DRd) group and median treatment duration of 21.3 months (range: 0.03 to 40.64 months) for the lenalidomide-dexamethasone group (Rd) in a Phase 3 active-controlled study MAIA.

The most frequent (≥20%) adverse reactions were

Serious adverse reactions with a 2% greater incidence in the DRd arm compared to the Rd arm were

Table 6: 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)
Any Grade
(%)
Grade 3
(%)
Grade 4
(%)
Any Grade
(%)
Grade 3
(%)
Grade 4
(%)
Infusion reactionsa 41 2 <1 0 0 0
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
General disorders and administration site conditions
  Peripheral edemab 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
Infections and infestations
  Upper respiratory tract infectionc 52 2 <1 36 2 <1
  Bronchitisd 29 3 0 21 1 0
  Pneumoniae 26 14 1 14 7 1
  Urinary tract infection 18 2 0 10 2 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
Musculoskeletal and connective tissue disorders
  Back pain 34 3 <1 26 3 <1
  Muscle spasms 29 1 0 22 1 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
Respiratory, thoracic and mediastinal disorders
  Dyspneaf 32 3 <1 20 1 0
  Coughg 30 <1 0 18 0 0
Vascular disorders
  Hypertensionh 13 6 <1 7 4 0
Key: D=daratumumab, Rd=lenalidomide-dexamethasone.
a Infusion reaction includes terms determined by investigators to be related to infusion, see section on Infusion Reactions below
b Generalized edema, Gravitational edema, Edema, Peripheral edema, Peripheral swelling
c Acute 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
d Bronchiolitis, Bronchitis, Bronchitis viral, Respiratory syncytial virus bronchiolitis, Tracheobronchitis
e Atypical pneumonia, Bronchopulmonary aspergillosis, Lung infection, Pneumocystis jirovecii infection, Pneumocystis jirovecii pneumonia, Pneumonia, Pneumonia aspiration, Pneumonia pneumococcal, Pneumonia viral, Pulmonary mycosis
f Dyspnea, Dyspnea exertional
g Cough, Productive cough
h Blood pressure increased, Hypertension

Laboratory abnormalities worsening during treatment from baseline listed in Table 7.

Table 7: Treatment-Emergent Hematology Laboratory Abnormalities in MAIA

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

Combination Treatment with Bortezomib, Melphalan and Prednisone
  • Adverse reactions described in Table 8 reflect exposure to Darzalex for a median treatment duration of 14.7 months (range: 0 to 25.8 months) for the daratumumab, bortezomib, melphalan and prednisone (D-VMP) group, and median treatment duration of 12 months (range: 0.1 to 14.9 months) for the VMP group in a Phase 3 active-controlled study ALCYONE.
  • The most frequent adverse reactions (≥20% with at least 5% greater frequency in the D-VMP arm) were infusion reactions, upper respiratory tract infection and edema peripheral.
  • 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 (D-VMP 5% vs VMP 1%), and
    • pulmonary edema (D-VMP 2% vs VMP 0%).

Table 8: 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)
Any Grade (%) Grade 3 (%) Grade 4 (%) Any Grade (%) Grade 3 (%) Grade 4 (%)
Infusion reactionsa 28 4 1 0 0 0
General disorders and administration site conditions
  Edema peripheralb 21 1 <1 14 1 0
Infections and infestations
  Upper respiratory tract infectionc 48 5 0 28 3 0
  Pneumoniad 16 12 <1 6 5 <1
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 Infusion reaction includes terms determined by investigators to be related to infusion, see section on Infusion Reactions below.
b edema peripheral, generalized edema, peripheral swelling
c 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.
d pneumonia, lung infection, pneumonia aspiration, pneumonia bacterial, pneumonia pneumococcal, pneumonia streptococcal, pneumonia viral, and pulmonary sepsis
e cough, productive cough
f dyspnea, dyspnea exertional
g hypertension, blood pressure increased

Laboratory abnormalities worsening during treatment from baseline listed in Table 9.

Table 9: Treatment-Emergent Hematology Laboratory Abnormalities in ALCYONE

  D-VMP (N=346) % VMP (N=354) %
Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4
Anemia 47 18 0 50 21 0
Thrombocytopenia 88 27 11 88 26 16
Neutropenia 86 34 10 87 32 11
Lymphopenia 85 46 12 83 44 9
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)
  • Adverse reactions described in Table 10 reflect exposure to Darzalex up to day 100 post-transplant in a Phase 3 active-controlled study CASSIOPEIA.
  • The median duration of induction/ASCT/consolidation treatment was 8.9 months (range: 7.0 to 12.0 months) for the DVTd group and 8.7 months (range: 6.4 to 11.5 months) for the VTd group.
  • The most frequent adverse reactions (>20% with at least 5% greater frequency in the DVTd group) were
    • infusion reactions,
    • nausea,
    • pyrexia,
    • upper respiratory tract infection and
    • bronchitis.
  • 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 10: 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)
Any Grade (%) Grade 3 (%) Grade 4 (%) Any Grade (%) Grade 3 (%) Grade 4 (%)
Infusion reactionsa 35 3 <1 0 0 0
Gastrointestinal disorders
  Nausea 30 4 0 24 2 <1
  Vomiting 16 2 0 10 2 0
General disorders and administration site conditions
  Pyrexia 26 2 <1 21 2 0
Infections and infestations
  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 reaction includes terms determined by investigators to be related to infusion, see section on Infusion Reactions below
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 11: Treatment-Emergent Hematology Laboratory Abnormalities in CASSIOPEIA

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

Relapsed/Refractory Multiple Myeloma

Combination Treatment with Lenalidomide and Dexamethasone
  • Adverse reactions described in Table 12 reflect exposure to Darzalex for a median treatment duration of 13.1 months (range: 0 to 20.7 months) for the daratumumab-lenalidomidedexamethasone (DRd) group and median treatment duration of 12.3 months (range: 0.2 to 20.1 months) for the lenalidomide-dexamethasone (Rd) group in a Phase 3 active-controlled study POLLUX.
  • The most frequent adverse reactions (≥20%) were
    • infusion reactions,
    • diarrhea,
    • nausea,
    • fatigue,
    • pyrexia,
    • upper respiratory tract infection,
    • muscle spasms,
    • cough and
    • dyspnea.
  • The overall incidence of serious adverse reactions was 49% for the DRd group compared with 42% for the Rd group.
  • 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 12: 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) %
Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4
Infusion reactionsa 48 5 0 0 0 0
Gastrointestinal disorders
  Diarrhea 43 5 0 25 3 0
  Nausea 24 1 0 14 0 0
  Vomiting 17 1 0 5 1 0
General disorders and administration site conditions
  Fatigue 35 6 <1 28 2 0
  Pyrexia 20 2 0 11 1 0
Infections and infestations
  Upper respiratory tract infectionb 65 6 <1 51 4 0
Musculoskeletal and connective tissue disorders
  Muscle spasms 26 1 0 19 2 0
Nervous system disorders
  Headache 13 0 0 7 0 0
Respiratory, thoracic and mediastinal disorders
  Coughc 30 0 0 15 0 0
  Dyspnead 21 3 <1 12 1 0
Key: D=daratumumab, Rd=lenalidomide-dexamethasone.
a Infusion reaction includes terms determined by investigators to be related to infusion, see section on Infusion Reactions below.
b 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
c cough, productive cough, allergic cough
d dyspnea, dyspnea exertional

Laboratory abnormalities worsening during treatment from baseline listed in Table 13.

Table 13: Treatment-Emergent Hematology Laboratory Abnormalities in POLLUX

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

Combination Treatment with Bortezomib and Dexamethasone
  • Adverse reactions described in Table 14 reflect exposure to Darzalex for a median treatment duration of 6.5 months (range: 0 to 14.8 months) in the daratumumab-bortezomibdexamethasone (DVd) group and median treatment duration of 5.2 months (range: 0.2 to 8.0 months) for the bortezomib-dexamethasone (Vd) group in a Phase 3 active-controlled study CASTOR.
  • The most frequent adverse reactions (>20%) were
    • infusion reactions,
    • diarrhea,
    • peripheral edema,
    • upper respiratory tract infection,
    • peripheral sensory neuropathy,
    • cough and
    • dyspnea.
  • The overall incidence of serious adverse reactions was 42% for the DVd group compared with 34% for the Vd group.
  • 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 14: 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) %
Any Grade Grade 3 Grade 4 Any Grades Grade 3 Grade 4
Infusion reactionsa 45 9 0 0 0 0
Gastrointestinal disorders
  Diarrhea 32 3 <1 22 1 0
  Vomiting 11 0 0 4 0 0
General disorders and administration site conditions
  Edema peripheralb 22 1 0 13 0 0
  Pyrexia 16 1 0 11 1 0
Infections and infestations
  Upper respiratory tract infectionc 44 6 0 30 3 <1
Nervous system disorders
  Peripheral sensory neuropathy 47 5 0 38 6 <1
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 reaction includes terms determined by investigators to be related to infusion, see section on Infusion Reactions below.
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 15.

Table 15: Treatment-Emergent Hematology Laboratory Abnormalities in CASTOR

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

Combination Treatment with Pomalidomide and Dexamethasone
  • Adverse reactions described in Table 16 reflect exposure to Darzalex, pomalidomide and dexamethasone (DPd) for a median treatment duration of 6 months (range: 0.03 to 16.9 months) in EQUULEUS.
  • The most frequent adverse reactions (>20%) were
  • 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 16: Adverse Reactions With Incidence ≥10% Reported in EQUULEUS

Body System
Adverse Reaction
DPd (N=103)
Any Grade (%) Grade 3 (%) Grade 4 (%)
  Infusion reactionsa 50 4 0
Gastrointestinal disorders
  Diarrhea 38 3 0
  Constipation 33 0 0
  Nausea 30 0 0
  Vomiting 21 2 0
General disorders and administration site conditions
  Fatigue 50 10 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 and infestations
  Upper respiratory tract infectionc 50 4 1
  Pneumoniad 15 8 2
Metabolism and nutrition disorders
  Hypokalemia 16 3 0
  Hyperglycemia 13 5 1
  Decreased appetite 11 0 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
Nervous system disorders
  Dizziness 21 2 0
  Tremor 19 3 0
  Headache 17 0 0
Psychiatric disorders
  Insomnia 23 2 0
  Anxiety 13 0 0
Respiratory, thoracic and mediastinal disorders
  Coughe 43 1 0
  Dyspneaf 33 6 1
  Nasal congestion 16 0 0
Key: D=Daratumumab, Pd=pomalidomide-dexamethasone.
a Infusion reaction includes terms determined by investigators to be related to infusion, see section on Infusion Reactions below.
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 17.

Table 17: Treatment-Emergent Hematology Laboratory Abnormalities in EQUULEUS

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

Monotherapy
  • The safety data reflect exposure to Darzalex in 156 adult patients with relapsed and refractory multiple myeloma treated with Darzalex at 16 mg/kg in three open-label, clinical trials.
  • 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 18. Table 19 describes Grade 3–4 laboratory abnormalities reported at a rate of ≥10%.

Table 18: Adverse Reactions With Incidence ≥10% in Patients With Multiple Myeloma Treated With Darzalex 16 mg/kg

  Darzalex 16 mg/kg
N=156
Incidence (%)
Adverse Reaction Any Grade Grade 3 Grade 4
  Infusion reactiona 48 3 0
General disorders and administration site conditions
  Fatigue 39 2 0
  Pyrexia 21 1 0
  Chills 10 0 0
Respiratory, thoracic and mediastinal disorders
  Cough 21 0 0
  Nasal congestion 17 0 0
  Dyspnea 15 1 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
Infections and infestations
  Upper respiratory tract infection 20 1 0
  Nasopharyngitis 15 0 0
  Pneumoniab 11 6 0
Gastrointestinal disorders
  Nausea 27 0 0
  Diarrhea 16 1 0
  Constipation 15 0 0
  Vomiting 14 0 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 reaction includes terms determined by investigators to be related to infusion, see section on Infusion Reactions below.
b Pneumonia also includes the terms streptococcal pneumonia and lobar pneumonia.

Table 19: Treatment-Emergent Grade 3-4 Laboratory Abnormalities (≥10%)

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

Infusion Reactions

  • In clinical trials (monotherapy and combination treatments; N=2,066) the incidence of any grade infusion reactions was 37% with the first (16 mg/kg, Week 1) infusion of Darzalex, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions.
  • Less than 1% of patients had a Grade 3/4 infusion reaction at Week 2 or subsequent infusions.
  • The median time to onset of a reaction was 1.5 hours (range: 0 to 72.8 hours). The incidence of infusion modification due to reactions was 36%.
  • Median durations of 16 mg/kg infusions for the 1st week, 2nd week and subsequent infusions were approximately 7, 4, and 3 hours respectively.
  • Severe infusion reactions included
  • Other adverse infusion reactions included
  • When Darzalex dosing was interrupted in the setting of ASCT (Study CASSIOPEIA) for a median of 3.75 months (range: 2.4; 6.9 months), upon re-initiation of Darzalex the incidence of IRRs was 11% for the first infusion following ASCT.
  • Infusion rate/dilution volume used upon re-initiation was that used for the last Darzalex infusion prior to interruption for ASCT. IRRs occurring at re-initiation of Darzalex following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4:<1%) with those reported in previous studies at Week 2 or subsequent infusions.
  • In EQUULEUS, patients receiving daratumumab combination treatment (n=97) were administered the first 16 mg/kg daratumumab dose at Week 1 split over two days i.e. 8 mg/kg on Day 1 and Day 2 respectively.
  • The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.
  • The median time to onset of a reaction was 1.8 hours (range: 0.1 to 5.4 hours).
  • The incidence of infusion interruptions due to reactions was 30%. Median durations of infusions were 4.2 h for Week 1-Day 1, 4.2 h for Week 1-Day 2, and 3.4 hours for the subsequent infusions.

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

  • In patients receiving Darzalex combination therapy, Grade 3 or 4 infections were reported as follows:
  • Relapsed/refractory patient studies: DVd: 21%, Vd: 19%; DRd: 27%, Rd: 23%; DPd: 28% 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 the active controlled studies, discontinuations from treatment due to infections (1-4%) and 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.

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 to daratumumab in the studies described below with the incidence of antibodies in other studies or to other 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 1,050 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 Darzalex. 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

What drugs interact with Darzalex (daratumumab)?

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 or genotyping.
  • Since the Kell blood group system is also sensitive to DTT treatment, K-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs.
  • If an emergency transfusion is required, non-cross-matched ABO/RhD-compatible RBCs can be given 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.

Summary

Darzalex (daratumumab) is monoclonal antibody used in combination with other medications to treat multiple myeloma. Common side effects of Darzalex include tiredness, nausea, diarrhea, shortness of breath, fever, cough, muscle spasms, back pain, cold-like symptoms (upper respiratory infection), nerve damage causing tingling, numbness or pain, swollen hands ankles or feet, constipation, trouble sleeping, joint pain, vomiting, chills, and dizziness. Darzalex may harm a fetus. It is unknown if Darzalex passes into breast milk.

Treatment & Diagnosis

Medications & Supplements

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Medically Reviewed on 1/27/2021
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.