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Multiple myeloma daratumumab subcutaneous

 Blood transfusion warning:


Interference with indirect antiglobulin tests may occur. Please notify your blood transfusion laboratory and send a blood sample for extended red blood cell phenotype and RBC antibody screen BEFORE the first dose of daratumumab.

If an emergency transfusion is required, non-cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices. Please refer to the ANZSBT/MSAG position paper. opens in a new tab or window  r

Patients with myeloma should be considered for inclusion into clinical trials. Link to ALLG website opens in a new tab or window and ANZCTR website opens in a new tab or window.

Link to Medical Scientific Advisory Group (MSAG) Clinical Practice Guideline Multiple Myeloma opens in a new tab or window

Link to MyeTxScheduler opens in a new tab or window developed by Myeloma Specialist Practice Network of the Haematology Society of Australia and New Zealand Nurses Group

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Cycle 1 and 2

Drug Dose Route Day
Daratumumab 1,800 mg Subcut 1, 8, 15, 22

Cycle 3 to 6

Drug Dose Route Day
Daratumumab 1,800 mg Subcut 1 and 15

Cycle 7 and further cycles

Drug Dose Route Day
Daratumumab 1,800 mg Subcut 1
Frequency:
28 days 
Cycles:
Continuous until disease progression or unacceptable toxicity.
Notes:
  • Post-injection dexamethasone may be omitted following the third injection if the patient experiences no major infusion-related reactions (IRRs).rr
  • For patients with a history of chronic obstructive pulmonary disease or asthma, consider the use of post-injection medications, including short and long-acting bronchodilators and inhaled corticosteroids. Inhaled post-injection medications may be discontinued following the fourth injection, at the discretion of the treating clinician if the patient experiences no major IRRs.r
Drug status:

Daratumumab: TGA registered but not PBS listed

Cost:
~ $49,010 for first cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1

Day 1
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 20 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.
Day 2 and 3
Dexamethasone 4 mg (PO) ONCE a day in the morning with or after food.*
Day 8
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 20 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.
Day 9 and 10
Dexamethasone 4 mg (PO) ONCE a day in the morning with or after food.*
Day 15
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.
Day 16 and 17
Dexamethasone 4 mg (PO) ONCE a day in the morning with or after food.*
Day 22
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

Cycle 2

Day 1, 8, 15, 22
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

Cycle 3 to 6

Day 1 and 15
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

Cycle 7 and further cycles

Day 1
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

* Post-injection dexamethasone may be omitted after the third injection if the patient experiences no major infusion-related reactions (IRRs).rr

For patients with a history of chronic obstructive pulmonary disease or asthma, consider the use of post-injection medications, including short and long-acting bronchodilators and inhaled corticosteroids. Inhaled post-injection medications may be discontinued following the fourth injection, at the discretion of the treating clinician if the patient experiences no major IRRs.r

Frequency:
28 days 
Cycles:
Continuous until disease progression or unacceptable toxicity.

Cycle 1 and 2

Drug Dose Route Day
Daratumumab 1,800 mg Subcut 1, 8, 15, 22

Cycle 3 to 6

Drug Dose Route Day
Daratumumab 1,800 mg Subcut 1 and 15

Cycle 7 and further cycles

Drug Dose Route Day
Daratumumab 1,800 mg Subcut 1
Frequency:
28 days 
Cycles:
Continuous until disease progression or unacceptable toxicity.
Notes:
  • Post-injection dexamethasone may be omitted following the third injection if the patient experiences no major infusion-related reactions (IRRs).rr
  • For patients with a history of chronic obstructive pulmonary disease or asthma, consider the use of post-injection medications, including short and long-acting bronchodilators and inhaled corticosteroids. Inhaled post-injection medications may be discontinued following the fourth injection, at the discretion of the treating clinician if the patient experiences no major IRRs.r
Drug status:

Daratumumab: TGA registered but not PBS listed

Cost:
~ $49,010 for first cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1

Day 1
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 20 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.
Day 2 and 3
Dexamethasone 4 mg (PO) ONCE a day in the morning with or after food.*
Day 8
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 20 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.
Day 9 and 10
Dexamethasone 4 mg (PO) ONCE a day in the morning with or after food.*
Day 15
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.
Day 16 and 17
Dexamethasone 4 mg (PO) ONCE a day in the morning with or after food.*
Day 22
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

Cycle 2

Day 1, 8, 15, 22
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (IV/PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

Cycle 3 to 6

Day 1 and 15
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

Cycle 7 and further cycles

Day 1
Paracetamol 1,000 mg (PO) 1 to 3 hours before treatment.
Loratadine 10 mg (PO) 1 to 3 hours before treatment.
Dexamethasone 12 mg (PO) 1 to 3 hours before treatment.
Daratumumab 1,800 mg (Subcut) via subcutaneous injection over 3 to 5 minutes.

* Post-injection dexamethasone may be omitted after the third injection if the patient experiences no major infusion-related reactions (IRRs).rr

For patients with a history of chronic obstructive pulmonary disease or asthma, consider the use of post-injection medications, including short and long-acting bronchodilators and inhaled corticosteroids. Inhaled post-injection medications may be discontinued following the fourth injection, at the discretion of the treating clinician if the patient experiences no major IRRs.r

Frequency:
28 days 
Cycles:
Continuous until disease progression or unacceptable toxicity.
  • Relapsed/refractory multiple myeloma after at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) or refractory to both a PI and an IMiD
Hypersensitivity/infusion-related reaction

High risk with daratumumab.

Infusion-Related Reactions (IRRs) can occur with administration of SC daratumumab. Hypersensitivity risk is greatest with the first dose of daratumumab, and is higher in IV than SC administration.r

Close monitoring during and for 4 hours after administration is recommended for cycle 1, dose 1 of SC daratumumab.r Given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards.rr

Read more about Hypersensitivity reaction
Pre and post-treatment medication

The product information states that pre- and post-treatment medication is required for this treatment.rr

Please refer to the treatment schedule for the suggested pre- and post-treatment medication regimen. This may be substituted to reflect institutional policy.

For patients with a history of chronic obstructive pulmonary disease, consider the use of post-treatment medications including short and long acting bronchodilators, and inhaled corticosteroids. Following the first four injections, if the patient experiences no major IRRs, these inhaled post-treatment medications may be discontinued at the discretion of the treating clinician.
Injection site reactions (ISRs)

Injection site reactions have been associated with subcutaneous daratumumab (pain, erythema, swelling etc.).
Inject into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel (umbilicus) over approximately 3-5 minutes. Injection sites should be rotated for successive injections. Consider the use of a single-use, winged infusion set.
Emetogenicity MINIMAL

No antiemetics should be routinely administered before treatment in patients without a history of nausea and vomiting. If patients experience nausea and/or vomiting, consider using the low antiemetic prophylaxis regimen.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Interference with indirect antiglobulin test (indirect Coombs test)

Daratumumab binds to CD38 found at low levels on red blood cells (RBCs) and may result in a positive indirect Coombs test.

Daratumumab-mediated positive indirect Coombs test may persist for up to 6 months after the last dose of daratumumab. Daratumumab bound to RBCs may cause panagglutination during pretransfusion indirect Coombs tests and may therefore mask detection of alloantibodies to red blood antigens in the patient’s serum. 

Extended red cell phenotyping and RBC antibody screen should be done for patients prior to starting daratumumab.

Please refer to the ANZSBT/MSAG position paper. opens in a new tab or window r
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), which can lead to false positive assay results in patients with IgG kappa myeloma protein. The initial assessment of complete responses by the International Myeloma Working Group (IMWG) criteria may be affected. 

For patients with persistent very good partial response other methods to evaluate the depth of response should be considered if it was to impact on management strategy.
Bone modifying agents

Use of a bone modifying agent (BMA) should be considered in all patients with symptomatic myeloma requiring treatment. For patients with newly diagnosed symptomatic myeloma, zoledronic acid, pamidronate or denosumab should be considered for monthly administration (adjust for kidney dysfunction where appropriate) for up to 2 years. A longer duration of therapy may be appropriate (MRC M IX trial).r

For more information, please see the following protocols:
ID 137 Multiple myeloma zoledronic acid
ID 147 Multiple myeloma pamidronate
ID 3964 Multiple myeloma denosumab - note denosumab is TGA approved but not PBS reimbursed for this indication.
Bisphosphonates and dental review

Caution should be taken with prolonged use of bisphosphonates due to the risk of osteonecrosis of the jaw (ONJ). A dental review prior to treatment is recommended, and all dental issues treated before the initiation of bisphosphonates. Dental review 6 to 12 monthly during treatment is advisable to minimise risk of ONJ. Concurrent daily oral supplements of calcium 500 mg and vitamin D 400 International Units are recommended.

Read more about medication-related osteonecrosis of the jaw (MRONJ)
Corticosteroids

Diabetic patients should monitor their blood glucose levels closely. To minimise gastric irritation, advise patient to take immediately after food. Consider the use of a H2 antagonist or proton pump inhibitor if appropriate.

Read more about acute short term effects from corticosteroids
Tumour lysis risk

Assess patient for risk of developing tumour lysis syndrome.

Read more about prevention and management of tumour lysis syndrome.
Pneumocystis jirovecii pneumonia (PJP) prophylaxis

­

Read more about prophylaxis of pneumocystis jiroveci (carinii) in cancer patients
Antiviral prophylaxis

Antiviral prophylaxis is recommended.

Read more about antiviral prophylaxis drugs and doses
Thromboprophylaxis

Thromboprophylaxis should be considered based on an individual benefit/risk assessment and at clinician discretion. 

Read more about the prophylaxis of venous thromboembolism (VTE) in multiple myeloma
Blood tests

FBC, EUC, eGFR, LFTs, calcium, magnesium and phosphate at baseline and prior to each treatment.
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease. Possible suboptimal response to inactivated vaccines.

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of fetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact of cancer treatment on fertility opens in a new tab or window
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) opens in a new tab or window unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Daratumumab:r

  • No dose reductions are recommended for daratumumab. Dose may be delayed until blood cell count recovery if haematological toxicity occurs.

Infusion-related reactions (IRRs):

  • Patients should be monitored and counselled regarding IRRs, especially during and following the first and second injections.
  • If an anaphylactic reaction or life-threatening (Grade 4) reactions occur, institute appropriate emergency care and permanently discontinue daratumumab SC.

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources:  

For more information see References & Disclaimer.

Daratumumab
No drug-drug interaction studies have been performed. Clinical pharmacokinetic assessments of daratumumab in combination with lenalidomide, pomalidomide, thalidomide, bortezomib and dexamethasone indicated no clinically-relevant drug-drug interaction
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inhibitors. If treating VTE, avoid use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window  inhibitors.

Dabigatran: avoid combination with strong P‑gp opens in a new tab or window inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update opens in a new tab or window

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Day 1

Subcutaneous injection

Pre treatment assessment

Check for adverse events during previous treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Check observations.

Pre treatment medication

Verify premedication has been taken as prescribed, see treatment schedule detail for suggested premedications.

Prior to administration

Allow daratumumab to come to room temperature before administration.

Subcutaneous daratumumab can result in injection reactions, consider the use of a single-use, winged infusion set.

Daratumumab

Administer daratumumab:
  • via subcutaneous injection over 3 to 5 minutes
  • alternate injection sites into the abdominal wall approximately 7.5 cm to the right or left of the navel (umbilicus), do not inject into other sites of the body.
Infusion-related reaction (IRR)

Manage first sign of anaphylaxis or severe IRR as per emergency. For all other IRRs notify a medical officer immediately.

Post daratumumab administration: 
  • patients should be monitored for 4 hours after cycle 1, dose 1 of SC daratumumab administration 
    • given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards
  • patients should be counselled regarding IRRs, especially during and following the first and second injections and about the possibility of delayed administration-related symptoms.

Post administration

Note: ensure the patient has post-daratumumab dexamethasone, if prescribed.

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Day 2 and 3

This is an oral treatment

Dexamethasone

Administer dexamethasone:
  • orally ONCE a day in the morning
  • with or immediately after food.

Note: if a dose is forgotten or vomited, contact treating team.

Day 8

Subcutaneous injection

Pre treatment assessment

Check for adverse events during previous treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Check observations.

Pre treatment medication

Verify premedication has been taken as prescribed, see treatment schedule detail for suggested premedications.

Prior to administration

Allow daratumumab to come to room temperature before administration.

Subcutaneous daratumumab can result in injection reactions, consider the use of a single-use, winged infusion set.

Daratumumab

Administer daratumumab:
  • via subcutaneous injection over 3 to 5 minutes
  • alternate injection sites into the abdominal wall approximately 7.5 cm to the right or left of the navel (umbilicus), do not inject into other sites of the body.
Infusion-related reaction (IRR)

Manage first sign of anaphylaxis or severe IRR as per emergency. For all other IRRs notify a medical officer immediately.

Post daratumumab administration: 
  • patients should be monitored for 4 hours after cycle 1, dose 1 of SC daratumumab administration 
    • given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards
  • patients should be counselled regarding IRRs, especially during and following the first and second injections and about the possibility of delayed administration-related symptoms.

Post administration

Note: ensure the patient has post-daratumumab dexamethasone, if prescribed.

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Day 9 and 10

This is an oral treatment

Dexamethasone

Administer dexamethasone:
  • orally ONCE a day in the morning
  • with or immediately after food.

Note: if a dose is forgotten or vomited, contact treating team.

Day 15

Subcutaneous injection

Pre treatment assessment

Check for adverse events during previous treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Check observations.

Pre treatment medication

Verify premedication has been taken as prescribed, see treatment schedule detail for suggested premedications.

Prior to administration

Allow daratumumab to come to room temperature before administration.

Subcutaneous daratumumab can result in injection reactions, consider the use of a single-use, winged infusion set.

Daratumumab

Administer daratumumab:
  • via subcutaneous injection over 3 to 5 minutes
  • alternate injection sites into the abdominal wall approximately 7.5 cm to the right or left of the navel (umbilicus), do not inject into other sites of the body.
Infusion-related reaction (IRR)

Manage first sign of anaphylaxis or severe IRR as per emergency. For all other IRRs notify a medical officer immediately.

Post daratumumab administration: 
  • patients should be monitored for 4 hours after cycle 1, dose 1 of SC daratumumab administration 
    • given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards
  • patients should be counselled regarding IRRs, especially during and following the first and second injections and about the possibility of delayed administration-related symptoms.

Post administration

Note: ensure the patient has post-daratumumab dexamethasone, if prescribed.

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Day 16 and 17

This is an oral treatment

Dexamethasone

Administer dexamethasone:
  • orally ONCE a day in the morning
  • with or immediately after food.

Note: if a dose is forgotten or vomited, contact treating team.

Day 22

Subcutaneous injection

Pre treatment assessment

Check for adverse events during previous treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Check observations.

Pre treatment medication

Verify premedication has been taken as prescribed, see treatment schedule detail for suggested premedications.

Prior to administration

Allow daratumumab to come to room temperature before administration.

Subcutaneous daratumumab can result in injection reactions, consider the use of a single-use, winged infusion set.

Daratumumab

Administer daratumumab:
  • via subcutaneous injection over 3 to 5 minutes
  • alternate injection sites into the abdominal wall approximately 7.5 cm to the right or left of the navel (umbilicus), do not inject into other sites of the body.
Infusion-related reaction (IRR)

Manage first sign of anaphylaxis or severe IRR as per emergency. For all other IRRs notify a medical officer immediately.

Post daratumumab administration: 
  • patients should be monitored for 4 hours after cycle 1, dose 1 of SC daratumumab administration 
    • given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards
  • patients should be counselled regarding IRRs, especially during and following the first and second injections and about the possibility of delayed administration-related symptoms.

Post administration

Note: ensure the patient has post-daratumumab dexamethasone, if prescribed.

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Discharge information

Discharge medications

Dexamethasone tablets - as/if prescribed, with written instructions on how to take them.

Antiemetics - as/if prescribed.

Prophylaxis medications - as/if prescribed, i.e. antivirals, PJP prophylaxis, tumour lysis prophylaxis.

Patient information

Ensure patient receives protocol patient information sheet.

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Days 1, 8, 15 and 22

Subcutaneous injection

Pre treatment assessment

Check for adverse events during previous treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Check observations.

Pre treatment medication

Verify premedication has been taken as prescribed, see treatment schedule detail for suggested premedications.

Prior to administration

Allow daratumumab to come to room temperature before administration.

Subcutaneous daratumumab can result in injection reactions, consider the use of a single-use, winged infusion set.

Daratumumab

Administer daratumumab:
  • via subcutaneous injection over 3 to 5 minutes
  • alternate injection sites into the abdominal wall approximately 7.5 cm to the right or left of the navel (umbilicus), do not inject into other sites of the body.
Infusion-related reaction (IRR)

Manage first sign of anaphylaxis or severe IRR as per emergency. For all other IRRs notify a medical officer immediately.

Post daratumumab administration: 
  • patients should be monitored for 4 hours after cycle 1, dose 1 of SC daratumumab administration 
    • given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards
  • patients should be counselled regarding IRRs, especially during and following the first and second injections and about the possibility of delayed administration-related symptoms.

Post administration

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Discharge information

Discharge medications

Dexamethasone tablets - as/if prescribed, with written instructions on how to take them.

Antiemetics - as/if prescribed.

Prophylaxis medications - as/if prescribed, i.e. antivirals, PJP prophylaxis, tumour lysis prophylaxis.

Patient information

Ensure patient receives protocol patient information sheet.

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Days 1 and 15

Subcutaneous injection

Pre treatment assessment

Check for adverse events during previous treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Check observations.

Pre treatment medication

Verify premedication has been taken as prescribed, see treatment schedule detail for suggested premedications.

Prior to administration

Allow daratumumab to come to room temperature before administration.

Subcutaneous daratumumab can result in injection reactions, consider the use of a single-use, winged infusion set.

Daratumumab

Administer daratumumab:
  • via subcutaneous injection over 3 to 5 minutes
  • alternate injection sites into the abdominal wall approximately 7.5 cm to the right or left of the navel (umbilicus), do not inject into other sites of the body.
Infusion-related reaction (IRR)

Manage first sign of anaphylaxis or severe IRR as per emergency. For all other IRRs notify a medical officer immediately.

Post daratumumab administration: 
  • patients should be monitored for 4 hours after cycle 1, dose 1 of SC daratumumab administration 
    • given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards
  • patients should be counselled regarding IRRs, especially during and following the first and second injections and about the possibility of delayed administration-related symptoms.

Post administration

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Discharge information

Discharge medications

Dexamethasone tablets - as/if prescribed, with written instructions on how to take them.

Antiemetics - as/if prescribed.

Prophylaxis medications - as/if prescribed, i.e. antivirals, PJP prophylaxis, tumour lysis prophylaxis.

Patient information

Ensure patient receives protocol patient information sheet.

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Day 1

Subcutaneous injection

Pre treatment assessment

Check for adverse events during previous treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Check observations.

Pre treatment medication

Verify premedication has been taken as prescribed, see treatment schedule detail for suggested premedications.

Prior to administration

Allow daratumumab to come to room temperature before administration.

Subcutaneous daratumumab can result in injection reactions, consider the use of a single-use, winged infusion set.

Daratumumab

Administer daratumumab:
  • via subcutaneous injection over 3 to 5 minutes
  • alternate injection sites into the abdominal wall approximately 7.5 cm to the right or left of the navel (umbilicus), do not inject into other sites of the body.
Infusion-related reaction (IRR)

Manage first sign of anaphylaxis or severe IRR as per emergency. For all other IRRs notify a medical officer immediately.

Post daratumumab administration: 
  • patients should be monitored for 4 hours after cycle 1, dose 1 of SC daratumumab administration 
    • given the low severity and incidence of IRRs, institutions could consider decreasing the period of post-administration observation from the second dose onwards
  • patients should be counselled regarding IRRs, especially during and following the first and second injections and about the possibility of delayed administration-related symptoms.

Post administration

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Discharge information

Discharge medications

Dexamethasone tablets - as/if prescribed, with written instructions on how to take them.

Antiemetics - as/if prescribed.

Prophylaxis medications - as/if prescribed, i.e. antivirals, PJP prophylaxis, tumour lysis prophylaxis.

Patient information

Ensure patient receives protocol patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Read more about hypersensitivity reaction 
Injection-site reactions

Inflammation of or damage to the tissue surrounding the area where a drug was injected.

Early (onset days to weeks)
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Arthralgia and myalgia

Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation. 

Read more about arthralgia and myalgia
Constipation
Diarrhoea

Read more about treatment induced diarrhoea
Dizziness

Feeling faint or lightheaded, weak or unsteady. Advise patients to stand up slowly from sitting down or lying down positions and increase fluid intake if dehydrated.
Dyspnoea
Fatigue

Read more about fatigue
Fever
Fluid retention and oedema

An excess amount of fluid around the cells, tissues or serous cavities of the body, leading to swelling.
Headache
Hypertension

High blood pressure is commonly associated with many anti-cancer drugs. Pre-existing hypertension should be controlled prior to initiation of drugs capable of causing hypertension.
Insomnia
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Peripheral neuropathy

Typically symmetrical sensory neuropathy, affecting the fingers and toes, sometimes progressing to the hands and feet.  It is associated with several classes of anti-cancer drugs. These include taxanes, platinum-based compounds, vinca alkaloids and some drugs used to treat multiple myeloma.

Read more about peripheral neuropathy
Respiratory tract infection
Side effects of corticosteroids

Insomnia, oedema, increased risk of infection e.g. oral thrush, gastric irritation, worsening of peptic ulcer disease, increased blood sugar levels, loss of diabetic control, mood and behavioural changes - including anxiety, euphoria, depression, mood swings, increased appetite and weight gain, osteoporosis and fractures (long term use), bruising and skin fragility are associated with corticosteroid use.
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Thromboembolism

Thromboembolic events, including pulmonary embolism, deep vein thrombosis and cerebrovascular accidents can occur. Thromboprophylaxis should be considered based on an individual benefit/risk assessment and at clinician discretion.

Read more about management of thromboembolism (VTE) in multiple myeloma

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia

Delayed (onset months to years)
Pulmonary toxicity

Pulmonary toxicity may include damage to the lungs, airways, pleura and pulmonary circulation. 

Read more about pulmonary toxicity associated with anti-cancer drugs

The evidence supporting this protocol is provided by a phase III, multicentre, international, open-label, non-inferiority, randomised trial (COLUMBA) involving 522 adult patients diagnosed with relapsed or refractory multiple myeloma (RRMM). The study tested the non-inferiority of subcutaneous (SC) daratumumab to intravenous(IV) daratumumab.r

Between Oct 31, 2017 and Dec 27, 2018, 522 patients were randomised 1:1 to receive either SC daratumumab (n=263) or IV daratumumab (n=259).

The co-primary endpoints were overall response and maximum trough concentration (cycle 3, day 1). The non-inferiority margin for overall response was defined using a 60% retention of the lower bound (20.8%) of the 95% confidence interval (CI) of the SIRIUS trial.r

SC daratumumab was shown to be non-inferior to IV daratumumab in terms of efficacy and pharmacokinetics and had an improved safety profile in patients with RRMM.r It was found to be well-tolerated and could be safely administered with fewer administration-related reactions.rr

Efficacy

After a median follow-up of 7.5 months (interquartile range (IQR) 6.5 - 9.3), an overall response was seen in 108 (41%) of the 263 patients in the SC group and in 96 (37%) of the 259 patients in the IV group (relative risk 1-11, 95% CI 0.89 to 1.37).

Figure 1: Responses according to IMWG criteriar

© Lancet Haematol 2020

Table 1: Survival outcomes after daratumumab treatmentr

Overall response Intravenous daratumumab Subcutaneous daratumumab p values
Median progression-free survival 6.1 months (95% CI 4.7 - 8.3) 5.6 months (95% CI 4.7 - 7.6) 0.93
6-month overall survival rate 83% (95% CI 78 - 87) 88% (95% CI 83 - 91) 0.60

Quality of life data was collected, with high levels of questionnaire completion (>88% in both treatment groups). Mean scores for “satisfaction with therapy” markers were consistently higher in the SC group than IV group and showed similarly favourable results when comparing expected and experienced side effects.

Toxicity

The most common grade 3 and 4 adverse events were anaemia (34 [13%] in the SC group and 36 [14%] in the IV group), neutropenia (34 [13%] and 20 [8%]), thrombocytopenia (36 [14%] and 35 [14%]) and pneumonia (7 [3%] and 11 [4%]). 

There was one death due to a treatment-related adverse event in the SC group (febrile neutropenia) and four in the IV group (sepsis [n=2], hepatitis B reactivation [n=1] and PJP [n=1]).

Table 2: Treatment-emergent adverse events r

  Intravenous daratumumab Subcutaneous daratumumab Significance
Infusion-related reactions 89/258 (34%) 33/260 (13%) OR 0.28, 95% CI 0.18-0.44, p<0.0001
Number of deaths due to treatment-related adverse events 4/258 (1.55%) 1/260 (0.38%) OR 0.25, 95% CI 0.03-2.20, p=0.2123
Number of patients discontinuing treatment due to adverse events 21/258 (8.1%) 18/260 (6.9%) OR 0.84, 95% CI 0.44-1.62, p=0.60
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Version 4

Date Summary of changes
27/02/2024

Protocol discussed by the Haematology Reference Committee alongside eviQ protocols containing daratumumab. The following change has been made:

  • Dexamethasone changed to PO/IV for all doses to reflect variations in local institutional practices

Version increased to V4.
23/04/2024 Daratumumab drug status updated to TGA registered but not PBS listed.

Version 3

Date Summary of changes
10/08/2023

Protocol updated with ADDIKD guideline recommendations. 

PDF of previous protocol.

Version number changed to V.3.
13/10/2023 Administration instructions for daratumumab amended to align with the drug product information.

Version 2

Date Summary of changes
13/06/2023

Dose of dexamethasone premed after initial 2 doses of daratumumab updated in Administration section to reflect treatment schedule

Version increased to V.2

Version 1

Date Summary of changes
14/10/2022 New protocol presented at the multiple myeloma Haematology Reference Committee meeting.
03/05/2023 Protocol approved and published as v.1. Review in 1 year.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/4084

04 Jun 2025