For relapsed or refractory multiple myeloma, after 1 prior therapy, POLLUX trial compared treatment with DARZALEX® + Rd vs Rd alone1

A multicenter, open-label, active-controlled phase 3 study1,2
  • A majority (86%) of patients received prior treatment with a proteasome inhibitor (PI)1
  • More than half (55%) of patients received prior treatment with an immunomodulatory agent1

Patients were refractory to prior therapies*1

  • 27% to the last line of treatment
  • 18% to a PI only
  • 21% to bortezomib

DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); IV=intravenous; PD=progressive disease; PO=by mouth; QW=once weekly; Q2W=every 2 weeks; Q4W=every 4 weeks; Rd=lenalidomide (R) + dexamethasone (d).

*Please note that this is not a full list of prior therapies reported at baseline and that lenalidomide-refractory patients were excluded from the study.2

Patient characteristics: baseline demographics were similar between arms1,2

ECOG PS=Eastern Cooperative Oncology Group Performance Status; Rd=lenalidomide (R) + dexamethasone (d).

The primary endpoint was progression-free survival (PFS) and the median follow-up was 13.5 months1,2

Efficacy was evaluated by PFS based on International Myeloma Working Group (IMWG) criteria.1

National Comprehensive Cancer Network® (NCCN®) Category 1, preferred

Daratumumab* (D) in combination with lenalidomide (R) and dexamethasone (d) is recommended by the NCCN Guidelines as a Category 1 preferred therapeutic option for patients with relapsed or refractory multiple myeloma

*Daratumumab includes both daratumumab and hyaluronidase-fihj (DARZALEX FASPRO®) for subcutaneous injection and daratumumab (DARZALEX®) for intravenous infusion. Daratumumab and hyaluronidase-fihj for subcutaneous injection has different dosing and administration instructions compared to daratumumab for intravenous infusion.

See NCCN.org for definitions of NCCN Categories of Preference and NCCN Categories of Evidence and Consensus.

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.2.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed November 2, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

DARZALEX® + Rd demonstrated superior efficacy vs Rd alone1

CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).

At a median follow-up of 13.5 months, median PFS was not reached with DARZALEX® + Rd triplet therapy vs 18.4 months with Rd1

Complete response rate more than doubled with DARZALEX® + Rd1

Almost all (91%) patients responded to DARZALEX® + Rd.

CR=complete response; ORR=overall response rate; PR=partial response; Rd=lenalidomide (R) + dexamethasone (d); sCR=stringent complete response; VGPR=very good partial response.

Deeper and sustained responses were demonstrated with DARZALEX® + Rd vs Rd1

With DARZALEX® + Rd, median time to first response was 1 month (range: 0.9 to 13 months).

Median duration of response was not yet reached with DARZALEX® + Rd (range: 1+ to 19.8+ months) vs 17.4 months with Rd (range: 1.4 to 18.5+ months), at a median follow-up of 13.5 months1

DARZALEX® + Rd safety profile
Adverse reactions with incidence ≥10%1

Rd=lenalidomide (R) + dexamethasone (d).

aUpper 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.

bInfusion-related reaction includes terms determined by investigators to be related to infusion.

cCough, productive cough, allergic cough.

dDyspnea, dyspnea exertional.

Note: Adverse reactions that occurred in >10% of patients and with at least 5% greater frequency in the DARZALEX® + Rd arm are listed.

  • Infusion reaction includes terms determined by investigators to be related to infusion. Severe infusion reactions included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision1
  • The most frequent adverse reactions (≥20%) with DARZALEX® + Rd (DRd) were infusion reactions, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasms, cough, and dyspnea1
  • Serious adverse reactions with at least a 2% greater incidence in the DARZALEX® + Rd 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)1
Treatment-emergent hematology laboratory abnormalities1

Rd=lenalidomide (R) + dexamethasone (d).

  • Grade 3/4 infections between study arms: 28% vs 23% with DARZALEX® + Rd and Rd, respectively2
  • Discontinuation rates due to adverse reactions with DARZALEX® + Rd were similar to Rd alone (7% vs 8%, respectively)1
Frequency of IRRs (any grade) across clinical trials (N=2,066)1
Chart showing recommended management of infusion-related reactions (IRRs)Chart showing recommended management of infusion-related reactions (IRRs)

IRR=infusion-related reaction.

Most IRRs occurred during the first infusion across clinical trials (N=2,066)1
  • For 37% of patients, IRRs (any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
  • Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
  • Incidence of infusion modification due to reactions was 36%
  • DARZALEX® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
  • Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®
Management of IRRs

For IRRs of any grade/severity, immediately interrupt the DARZALEX® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX® as outlined below.1

IRR=infusion-related reaction.

Interference with serological testing1

DARZALEX® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX® infusion.

Reminders

  • Type and screen patients before starting DARZALEX®
  • Inform blood banks when a patient is on DARZALEX®
  • Identify any blood samples of patients treated with DARZALEX®
  • Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Neutropenia and thrombocytopenia1
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
Interference with determination of complete response1
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
Embryo-fetal toxicity1
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® 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® and for 3 months after the last dose.
The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

Brochure on daratumumab and serological testing

Download brochure

Identification card to give to patients taking daratumumab

Download ID card

For relapsed or refractory multiple myeloma, after 1 prior therapy, CASTOR trial compared treatment with DARZALEX® + Vd vs Vd alone1

A multicenter, open-label, active-controlled, phase 3 study1,2

DVd=DARZALEX® (D) + bortezomib (V) + dexamethasone (d); ECOG PS=Eastern Cooperative Oncology Group Performance Status; Vd=bortezomib (V) + dexamethasone (d).

  • A majority (76%) of patients received prior treatment with an immunomodulatory agent1
  • More than half (69%) of patients received prior treatment with a proteasome inhibitor (PI)1

Patients were refractory to prior therapies*1

  • 32% to the last line of treatment
  • 33% to an immunomodulatory agent only
    • 24% in the DARZALEX® + Vd arm and 33% in the Vd arm to lenalidomide

Vd=bortezomib (V) + dexamethasone (d).

*Please note that this is not a full list of prior therapies reported at baseline and that bortezomib-refractory patients were excluded from the study.

Patient characteristics: baseline demographics were similar between arms1

ECOG PS=Eastern Cooperative Oncology Group Performance Status; Vd=bortezomib (V) + dexamethasone (d).

The primary endpoint was progression-free survival (PFS) and the median follow-upwas 7.4 months1,2

Efficacy was evaluated by PFS based on International Myeloma Working Group (IMWG) criteria.1

National Comprehensive Cancer Network® (NCCN®) Category 1, preferred

Daratumumab* (D) in combination with bortezomib (V) and dexamethasone (d) is recommended by the NCCN Guidelines as a Category 1 preferred therapeutic option for patients with relapsed or refractory multiple myeloma

*Daratumumab includes both daratumumab and hyaluronidase-fihj (DARZALEX FASPRO®) for subcutaneous injection and daratumumab (DARZALEX®) for intravenous infusion. Daratumumab and hyaluronidase-fihj for subcutaneous injection has different dosing and administration instructions compared to daratumumab for intravenous infusion.

See NCCN.org for definitions of NCCN Categories of Preference and NCCN Categories of Evidence and Consensus.

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.2.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed November 2, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

DARZALEX® + Vd demonstrated superior efficacy vs Vd alone1

CI=confidence interval; DVd=DARZALEX® (D) + bortezomib (V) + dexamethasone (d); HR=hazard ratio; PFS=progression-free survival; Vd=bortezomib (V) + dexamethasone (d).

Median PFS had not yet been reached with DARZALEX® + Vd triplet therapy vs 7.2 months with Vd1

Complete response rate more than doubled with DARZALEX® + Vd1

The majority (79%) of patients responded to DARZALEX® + Vd.

CR=complete response; ORR=overall response rate; PR=partial response; sCR=stringent complete response; Vd=bortezomib (V) + dexamethasone (d); VGPR=very good partial response.

Deeper and sustained responses were demonstrated with DARZALEX® + Vd vs Vd1

With DARZALEX® + Vd, median time to first response was 0.8 months (range: 0.7 to 4 months).

Median duration of response was not yet reached with DARZALEX® + Vd (range: 1.4+ to 14.1+ months) vs 7.9 months with Vd (range: 1.4+ to 12+ months), at a median follow-up of 7.4 months1

Established safety profile of DARZALEX® + Vd
Adverse reactions with incidence ≥10%1

Vd=bortezomib (V) + dexamethasone (d).

aInfusion-related reaction includes terms determined by investigators to be related to infusion.

bUpper 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.

cCough, productive cough, allergic cough.

dEdema peripheral, edema, generalized edema, peripheral swelling.

eDyspnea, dyspnea exertional.

Note: Adverse reactions that occurred in >10% of patients and with at least 5% greater frequency in the DARZALEX® + Vd arm are listed.

  • Infusion reaction includes terms determined by investigators to be related to infusion. Severe infusion reactions included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision1
  • The most frequent adverse reactions (>20%) with DARZALEX® + Vd (DVd) were infusion reactions, diarrhea, peripheral edema, upper respiratory tract infection, peripheral sensory neuropathy, cough, and dyspnea1
  • 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)1
Treatment-emergent hematology laboratory abnormalities1

Vd=bortezomib (V) + dexamethasone (d).

  • Grade 3/4 infections were similar between study arms: 21% vs 19% with DARZALEX® + Vd and Vd, respectively2
  • Discontinuation rates due to adverse reactions with DARZALEX® + Vd were similar to Vd alone (7% vs 9%, respectively)1
Frequency of IRRs (any grade) across clinical trials (N=2,066)1
Chart showing recommended management of infusion-related reactions (IRRs)Chart showing recommended management of infusion-related reactions (IRRs)

IRR=infusion-related reaction.

Most IRRs occurred during the first infusion across clinical trials (N=2,066)1
  • For 37% of patients, IRRs (any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
  • Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
  • Incidence of infusion modification due to reactions was 36%
  • DARZALEX® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
  • Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®
Management of IRRs

For IRRs of any grade/severity, immediately interrupt the DARZALEX® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX® as outlined below.1

IRR=infusion-related reaction.

Interference with serological testing1

DARZALEX® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX® infusion.

Reminders

  • Type and screen patients before starting DARZALEX®
  • Inform blood banks when a patient is on DARZALEX®
  • Identify any blood samples of patients treated with DARZALEX®
  • Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Neutropenia and thrombocytopenia1
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
Interference with determination of complete response1
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
Embryo-fetal toxicity1
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® 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® and for 3 months after the last dose.
The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

Brochure on daratumumab and serological testing

Download brochure

Identification card to give to patients taking daratumumab

Download ID card

For relapsed or refractory multiple myeloma, after 1 to 3 prior therapies, CANDOR and EQUULEUS trials evaluated treatment with DARZALEX® + Kd1

CANDOR: phase 3, randomized, open-label, multicenter study comparing twice weekly DARZALEX® + Kd vs twice weekly Kd alone1,2

ANC=absolute neutrophil count; BIW=twice weekly; DKd=DARZALEX® (D) + carfilzomib (K) + dexamethasone (d); IV=intravenous; Kd=carfilzomib (K) + dexamethasone (d); PD=progressive disease; QW=weekly; Q2W=every 2 weeks; Q4W=every 4 weeks.

*For patients aged >75 years on a reduced dexamethasone dose of 20 mg, the entire 20 mg dose was given as pre-medication on days when DARZALEX® was administered.1

Patient characteristics1
  • The median age was 64 years (range: 29–84 years); 58% male; 79% White, 14% Asian, and 2% Black
  • Patients had received a median of 2 prior lines of therapy and 58% of patients had received prior autologous stem cell transplantation (ASCT)
  • 92% received a prior proteasome inhibitor (PI), and of those, 34% were refractory to a PI-including regimen
  • 42% of patients had received prior lenalidomide, and of those, 33% were refractory to a lenalidomide-containing regimen

EQUULEUS: an open-label, multicohort study of once-weekly DARZALEX® + Kd1

EQUULEUS evaluated the efficacy and safety of DARZALEX® in combination with once-weekly carfilzomib (70 mg/m2) and dexamethasone in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy.

Baseline patient characteristics (n=85)1

Chart showing recommended management of infusion-related reactions (IRRs)Chart showing recommended management of infusion-related reactions (IRRs)

PI=proteasome inhibitor.

National Comprehensive Cancer Network® (NCCN®) Category 1, preferred

Daratumumab* (D) in combination with carfilzomib (K) and dexamethasone (d) is recommended by the NCCN Guidelines as a Category 1 preferred therapeutic option for patients with relapsed or refractory multiple myeloma

*Daratumumab includes both daratumumab and hyaluronidase-fihj (DARZALEX FASPRO®) for subcutaneous injection and daratumumab (DARZALEX®) for intravenous infusion. Daratumumab and hyaluronidase-fihj for subcutaneous injection has different dosing and administration instructions compared to daratumumab for intravenous infusion.

See NCCN.org for definitions of NCCN Categories of Preference and NCCN Categories of Evidence and Consensus.

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.2.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed November 2, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

CANDOR: DARZALEX® + Kd demonstrated superior efficacy vs Kd alone1

CI=confidence interval; DKd=DARZALEX® (D) + carfilzomib (K) + dexamethasone (d); HR=hazard ratio; Kd=carfilzomib (K) + dexamethasone (d); PFS=progression-free survival.

PFS was assessed by an independent review committee (IRC) using International Myeloma Working Group (IMWG) response criteria.1

At a median follow-up of 16.9 months and 16.3 months, respectively, the median PFS had not yet been reached for DARZALEX® + Kd vs 15.8 months with Kd alone1,2
Significant improvement in overall response rate (ORR) with DARZALEX® + Kd1

CI=confidence interval; CR=complete response; DKd=DARZALEX® (D) + carfilzomib (K) + dexamethasone (d); Kd=carfilzomib (K) + dexamethasone (d); ORR=overall response rate; PR=partial response; VGPR=very good partial response.

*DKd (95% CI: 80, 88).

Kd (95% CI: 67, 81).

Superior minimal residual disease (MRD) negativity* with DARZALEX® + Kd vs Kd alone1

CI=confidence interval; CR=complete response; DKd=DARZALEX® (D) + carfilzomib (K) + dexamethasone (d); Kd=carfilzomib (K) + dexamethasone (d); MRD=minimal residual disease.

*Based on a sensitivity threshold of 10-5 using a next-generation sequencing assay (clonoSEQ®). MRD negativity was defined according to the 2016 International Myeloma Working Group Uniform Response Criteria (IMWG-URC).

DKd (95% CI: 9, 17).

Kd (95% CI: 0.2, 4.6).

§P value from the stratified Cochran-Mantel-Haenszel Chi-Square test.

EQUULEUS: demonstrated response with once weekly DARZALEX® + Kd1

CI=confidence interval; CR=complete response; Kd=carfilzomib (K) + dexamethasone (d); PR=partial response; sCR=stringent complete response; VGPR=very good partial response.

CANDOR: DARZALEX® + Kd safety profile

Most frequent adverse reactions reported in ≥15% of patients who received DARZALEX® + Kd1

DKd=DARZALEX® (D) + carfilzomib (K) + dexamethasone (d); Kd=carfilzomib (K) + dexamethasone (d).

aThe 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.

bRespiratory tract infection includes respiratory tract infection, lower respiratory tract infection, upper respiratory tract infection, and viral upper respiratory tract infection.

cThrombocytopenia includes platelet count decreased and thrombocytopenia.

dAnemia includes anemia, hematocrit decreased, and hemoglobin decreased.

eFatigue includes fatigue and asthenia.

fCough includes productive cough and cough.

gIncludes fatal adverse reactions.

  • Median treatment duration of 16.1 months (range: 0.1–23.7) with DKd and 9.3 months (range: 0.1–22.4 months) in Kd1
  • Serious adverse reactions occurred in 56% of patients who received DARZALEX® in combination with Kd and 46% of patients who received Kd alone1
  • 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%)1
  • Permanent discontinuation of DARZALEX® due to an adverse reaction occurred in 9% of patients1
  • 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 vs 5% of 153 patients who received Kd, and the most frequent fatal adverse reaction was infection (4.5% vs 2.6%)1

EQUULEUS: DARZALEX® + Kd safety profile

Most frequent adverse reactions reported in ≥15% of patients receiving DARZALEX® + once weekly carfilzomib and dexamethasone1

DKd=DARZALEX® (D) + carfilzomib (K) + dexamethasone (d); Kd=carfilzomib (K) + dexamethasone (d).

aThrombocytopenia includes platelet count decreased and thrombocytopenia.

bFatigue includes fatigue and asthenia.

cThe 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.

dRespiratory tract infection includes respiratory tract infection, lower respiratory tract infection, upper respiratory tract infection, and viral upper respiratory tract infection.

eAnemia includes anemia, hematocrit decreased, and hemoglobin decreased.

fCough includes productive cough and cough.

gNeutropenia includes neutrophil count decreased and neutropenia.

hLymphopenia includes lymphocyte count decreased and lymphopenia.

  • Median treatment duration of 19.8 months (range: 0.3–34.5 months)1
  • Serious adverse reactions were reported in 48% of patients1
  • 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%)1
  • Permanent discontinuation of DARZALEX® due to an adverse reaction occurred in 8% of patients1
  • 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 progression1

DARZALEX® + Kd infusion-related reactions1

  • Infusion-related reactions (IRRs) occurred in 41% of patients; 12% were Grade 3 or 4
  • IRRs of any grade or severity may require management by interruption, modification, and/or discontinuation of the infusion
  • Most IRRs occurred during the first infusion
Frequency of IRRs (any grade) across clinical trials (N=2,066)1
Chart showing recommended management of infusion-related reactions (IRRs)Chart showing recommended management of infusion-related reactions (IRRs)

IRR=infusion-related reaction.

Most IRRs occurred during the first infusion across clinical trials (N=2,066)1
  • For 37% of patients, IRRs (any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
  • Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
  • Incidence of infusion modification due to reactions was 36%
  • DARZALEX® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
  • Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®
Management of IRRs

For IRRs of any grade/severity, immediately interrupt the DARZALEX® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX® as outlined below.1

IRR=infusion-related reaction.

Interference with serological testing1

DARZALEX® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX® infusion.

Reminders

  • Type and screen patients before starting DARZALEX®
  • Inform blood banks when a patient is on DARZALEX®
  • Identify any blood samples of patients treated with DARZALEX®
  • Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Neutropenia and thrombocytopenia1
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
Interference with determination of complete response1
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
Embryo-fetal toxicity1
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® 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® and for 3 months after the last dose.
The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

Brochure on daratumumab and serological testing

Download brochure

Identification card to give to patients taking daratumumab

Download ID card

For relapsed or refractory multiple myeloma, after 2 prior therapies, EQUULEUS trial evaluated treatment with DARZALEX® + Pd1

An open-label, multi-cohort study

Patients had received prior treatment with a proteasome inhibitor (PI) and an immunomodulatory agent1

  • This trial included 103 patients who received DARZALEX® 16 mg/kg in combination with Pd and were treated with pre- and post-infusion medications. Patients were treated until disease progression or unacceptable toxicity1
  • Patients had a median of 4 prior lines of therapy1
  • Of the patients who were tested for cytogenetics, 74.7% were standard risk and 25.3% were high risk2

Patients were refractory to prior therapies*1

  • 89% to lenalidomide
  • 71% to bortezomib
  • 64% to bortezomib and lenalidomide

DPd=DARZALEX® (D) + pomalidomide (P) + dexamethasone (d); Pd=pomalidomide (P) + dexamethasone (d).

*Please note that this is not a full list of prior therapies.

Patient characteristics2

ECOG PS=Eastern Cooperative Oncology Group Performance Status.

National Comprehensive Cancer Network® (NCCN®) Category 1, preferred

Daratumumab* (D) in combination with pomalidomide (P) and dexamethasone (d) is recommended by the NCCN Guidelines as a Category 1 preferred therapeutic option for patients with relapsed or refractory multiple myeloma, after 1 prior therapy‡§

*Daratumumab includes both daratumumab and hyaluronidase-fihj (DARZALEX FASPRO®) for subcutaneous injection and daratumumab (DARZALEX®) for intravenous infusion. Daratumumab and hyaluronidase-fihj for subcutaneous injection has different dosing and administration instructions compared to daratumumab for intravenous infusion.

See NCCN.org for definitions of NCCN Categories of Preference and NCCN Categories of Evidence and Consensus.

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.2.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed November 2, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

§DARZALEX FASPRO® + Pd is FDA-approved in patients who have received ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI). DARZALEX® + Pd is FDA-approved in patients who have received ≥2 prior lines of therapy including lenalidomide and a PI.1,3

Efficacy demonstrated with DARZALEX® + Pd

CI=confidence interval; CR=complete response; ORR=overall response rate; Pd=pomalidomide (P) + dexamethasone (d); PR=partial response; sCR=stringent complete response; VGPR=very good partial response.

*Efficacy results were based on ORR as determined by an Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) criteria.1

Median time to response

  • With DARZALEX® + Pd (n=61), median time to response was 1 month (range: 0.9 to 2.8 months)1
Median duration of response with DARZALEX® + Pd was 13.6 months (range: 0.9+ to 14.6+ months)1

DARZALEX® + Pd safety profile

Adverse reactions with incidence ≥10%1

Pd=pomalidomide (P) + dexamethasone (d).

aInfusion-related reaction includes terms determined by investigators to be related to infusion.

bEdema, edema peripheral, peripheral swelling.

cAcute tonsillitis, bronchitis, laryngitis, nasopharyngitis, pharyngitis, respiratory syncytial virus infection, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection.

dLung infection, pneumonia, pneumonia aspiration.

eCough, productive cough, allergic cough.

fDyspnea, dyspnea exertional.

  • Infusion reaction includes terms determined by investigators to be related to infusion. Severe infusion reactions included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision1
  • The most frequent adverse reactions (≥20%) with DARZALEX® + Pd (DPd) were infusion reactions, diarrhea, constipation, nausea, vomiting, fatigue, pyrexia, upper respiratory tract infection, muscle spasms, back pain, arthralgia, dizziness, insomnia, cough, and dyspnea1
  • The overall incidence of serious adverse reactions was 49%. Serious adverse reactions reported in ≥5% of patients included pneumonia (7%)1

Treatment-emergent hematology laboratory abnormalities1

Pd=pomalidomide (P) + dexamethasone (d).

  • The discontinuation rate due to adverse reactions with DARZALEX® + Pd was 13%1
Frequency of IRRs (any grade) across clinical trials (N=2,066)1
Chart showing recommended management of infusion-related reactions (IRRs)Chart showing recommended management of infusion-related reactions (IRRs)

IRR=infusion-related reaction.

Most IRRs occurred during the first infusion across clinical trials (N=2,066)1
  • For 37% of patients, IRRs (any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
  • Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
  • Incidence of infusion modification due to reactions was 36%
  • DARZALEX® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
  • Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®
Management of IRRs

For IRRs of any grade/severity, immediately interrupt the DARZALEX® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX® as outlined below.1

IRR=infusion-related reaction.

Interference with serological testing1

DARZALEX® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX® infusion.

Reminders

  • Type and screen patients before starting DARZALEX®
  • Inform blood banks when a patient is on DARZALEX®
  • Identify any blood samples of patients treated with DARZALEX®
  • Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Neutropenia and thrombocytopenia1
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
Interference with determination of complete response1
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
Embryo-fetal toxicity1
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® 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® and for 3 months after the last dose.
The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

Brochure on daratumumab and serological testing

Download brochure

Identification card to give to patients taking daratumumab

Download ID card

For relapsed or refractory multiple myeloma, after 3 prior therapies, SIRIUS trial evaluated treatment with DARZALEX® monotherapy1

A phase 2, single-arm, open-label, multicenter trial in heavily pretreated patients2

All patients received prior treatment with a proteasome inhibitor (PI) and an immunomodulatory agent.2

Median number of prior therapies: 51

Patients were refractory to prior therapies*1

  • 97% to the last line of treatment
  • 95% to both a PI and an immunomodulatory agent
  • 90% to bortezomib
  • 88% to lenalidomide
  • 77% to alkylating agents

*Please note that this is not a full list of prior therapies.

Patient characteristics

ECOG PS=Eastern Cooperative Oncology Group Performance Status.

This trial included 106 patients with relapsed or refractory multiple myeloma who were administered pre- and post-infusion medications and treated with DARZALEX® 16 mg/kg until unacceptable toxicity or disease progression.1

National Comprehensive Cancer Network® (NCCN®) Category 2A, useful in certain circumstances

Daratumumab* (D) monotherapy is recommended by the NCCN Guidelines as a Category 2A, useful in certain circumstances therapeutic option for patients with relapsed or refractory multiple myeloma, after 3 prior therapies

*Daratumumab includes both daratumumab and hyaluronidase-fihj (DARZALEX FASPRO®) for subcutaneous injection and daratumumab (DARZALEX®) for intravenous infusion. Daratumumab and hyaluronidase-fihj for subcutaneous injection has different dosing and administration instructions compared to daratumumab for intravenous infusion.

See NCCN.org for definitions of NCCN Categories of Preference and NCCN Categories of Evidence and Consensus.

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.2.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed November 2, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Overall response rate (ORR) with DARZALEX® monotherapy*1

CI=confidence interval; ORR=overall response rate; PR=partial response; sCR=stringent complete response;

VGPR=very good partial response.

  • DARZALEX® achieved sCR + VGPR in 12% of patients1

*Efficacy results were based on ORR as determined by an Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) criteria.1

DARZALEX® provided a 7.4-month median duration of response (range: 1.2 to 13.1+ months)1

Median duration of response

Median time to response was 1 month (range: 0.9 to 5.6 months)1

DARZALEX® monotherapy safety profile

Adverse reactions with incidence ≥10%1

aInfusion-related reaction includes terms determined by investigators to be related to infusion.

bPneumonia also includes the terms streptococcal pneumonia and lobar pneumonia.

  • Infusion reaction includes terms determined by investigators to be related to infusion. Severe infusion reactions included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision1
  • Safety data were pooled from 3 open-label clinical studies of relapsed or refractory patients treated with DARZALEX® 16 mg/kg (n=156)1
4% of patients discontinued treatment due to adverse reactions; adverse reactions resulted in treatment delay for 24 patients (15%), most frequently for infections1

Treatment-emergent Grade 3/4 laboratory abnormalities (≥10%)1

Frequency of IRRs (any grade) across clinical trials (N=2,066)1
Chart showing recommended management of infusion-related reactions (IRRs)Chart showing recommended management of infusion-related reactions (IRRs)

IRR=infusion-related reaction.

Most IRRs occurred during the first infusion across clinical trials (N=2,066)1
  • For 37% of patients, IRRs (any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
  • Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
  • Incidence of infusion modification due to reactions was 36%
  • DARZALEX® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
  • Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®
Management of IRRs

For IRRs of any grade/severity, immediately interrupt the DARZALEX® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX® as outlined below.1

IRR=infusion-related reaction.

Interference with serological testing1

DARZALEX® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX® infusion.

Reminders

  • Type and screen patients before starting DARZALEX®
  • Inform blood banks when a patient is on DARZALEX®
  • Identify any blood samples of patients treated with DARZALEX®
  • Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Neutropenia and thrombocytopenia1
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
Interference with determination of complete response1
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
Embryo-fetal toxicity1
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® 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® and for 3 months after the last dose.
The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

Brochure on daratumumab and serological testing

Download brochure

Identification card to give to patients taking daratumumab

Download ID card

NCCN Guidelines recommendations for daratumumab-containing regimens