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DARZALEX® + bortezomib + cyclophosphamide + dexamethasone (DVCd)

For newly-diagnosed AL amyloidosis

DARZALEX® in combination with bortezomib, cyclophosphamide and dexamethasone (VCd) is the first and only targeted therapy to significantly transform clinical outcomes in AL amyloidosis*[1]

Study design

ANDROMEDA is a randomised, open-label, active-controlled, multicentre, phase 3 study comparing DARZALEX® + VCd (DVCd) vs. VCd (N=388).[1]


* DVCd vs. VCd alone.

Efficacy

NEW DATA │ANDROMEDA study presented at ASH 2021

Median follow-up: 25.8 months[1][2]

Haematologic complete response (CR)

Major organ deterioration progression-free survival

Organ response at 18 months

complete-response-53-3pc@1x
organ-deterioration-42pc@1x
organ-response-6months@1x
Subgroup analyses

DVCd provided consistent benefit across the majority of patient subgroups in a pre-specified analysis of haematologic CR, including:*[1][2]

  • Baseline renal function
  • Baseline cardiac involvement
  • Baseline cytogenetic risk

* DVCd vs. VCd alone.

Safety Profile

DARZALEX® + VCd offers a consistent and well-characterised safety profile*[1][3]
  • Discontinuation rates were low for DVCd and VCd 5% vs. 4%, respectively[2]
  • Rates of administration-related reactions (ARR) and injection-site reactions (ISR) were low with DARZALEX® SC + VCd:[1]
  • Systemic ARRs occurred in 7.3% of patients receiving DVCd – all were Grade 1 or 2, and most (86%) occurred during the first administration
  • ISRs occurred in 28.0% of patients receiving DARZALEX® SC + VCd patients and 23.9% of patients receiving VCd

* DVCd vs. VCd alone.

Dosing

DARZALEX® SC + VCd dosing schedule: 4-week cycle regimen[1][3]

Treatment

Dose

Dosing schedule

DARZALEX® (daratumumab)

1800 mg SC

Cycles 1–2: Weekly (total of 8 doses)

Cycles 3–6: Every 2 weeks (total of 8 doses)

Cycles 7+: Every 4 weeks until disease progression

Bortezomib

1.3 mg/m2 SC body surface area

Weekly on Days 1, 8, 15, and 22 of repeated 28-day/4-week cycles

Cyclophosphamide
300 mg/m2 PO/IV*
Weekly on Days 1, 8, 15, and 22 of repeated 28-day/4-week cycles
Dexamethasone

40 mg PO/IV*

Weekly on Days 1, 8, 15, and 22 of repeated 28-day/4-week cycles

* On DARZALEX® SC injection days, 20 mg of the dexamethasone was given as a pre-injection medication and the remainder given the day after the injection.[1] In the phase 3 clinical trial, dexamethasone was administered at a reduced dose of 20 mg/week for patients >70 years, BMI <18.5 kg/m2, or those who have hypervolemia, poorly controlled diabetes mellitus, or prior intolerance to steroid therapy.

Dosing schedule – newly-diagnosed AL amyloidosis
DVCd dosing schedule: 4-week cycle regimen[1]

DVCd dosing schedule

(PDF, xx KB)

Recommended concomitant medications & missed dose information[3]

Pre-injection[3]

Medications should be administered to reduce the risk of IRRs to all patients 1–3 hours prior to every DARZALEX® SC injection as follows:

  • Corticosteroid (long-acting or intermediate-acting) – dexamethasone 20 mg or equivalent administered before every DARZALEX® injection
  • When dexamethasone is the background regimen-specific corticosteroid, the dexamethasone treatment dose will instead serve as pre-injection medicinal product on DARZALEX® administration days
  • Additional background regimen–specific corticosteroids (e.g., prednisone) should not be taken on DARZALEX® administration days when patients have received dexamethasone (or equivalent) as a pre-injection medication
  • Antipyretic – paracetamol 650–1000 mg
  • Antihistamine – diphenhydramine 25–50 mg PO/IV or equivalent
Post-injection[3]

Medications should be administered to reduce the risk of delayed IRRs as follows:

  • Consider administering low-dose methylprednisolone (≤20 mg) or equivalent the day after the DARZALEX® injection. However, if a background regimen–specific corticosteroid (e.g., dexamethasone, prednisone) is administered the day after the DARZALEX® injection, additional post-injection medications may not be needed
  • If the patient experiences no major IRRs after the first three injections, post-injection corticosteroids (excluding any background regimen corticosteroids) may be discontinued
Additional concomitant medications[3]

Patients with a history of COPD[3]

  • For patients with a history of chronic obstructive pulmonary disease, the use of post-injection medications, including short- and long-acting bronchodilators, and inhaled corticosteroids, should be considered. Following the first four injections, if the patient experiences no major IRRs, these inhaled post-injection medications may be discontinued at the discretion of the physician

Herpes zoster prophylaxis[3]

  • Anti-viral prophylaxis should be considered for the prevention of herpes zoster virus reactivation
Missed dose[3]

If a planned dose of DARZALEX® is missed, the dose should be administered as soon as possible, and the dosing schedule should be adjusted accordingly, maintaining the treatment interval

Dose modifications[3]

No dose reductions of DARZALEX® are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of haematological toxicity

IRR management

As is the case for all monoclonal antibodies, DARZALEX® is associated with IRRs, although not everybody will experience one.[4]

In clinical trials with DARZALEX® SC formulation (monotherapy and combination treatments; N=683), the incidence of any Grade IRRs was 8.2% with the first injection of DARZALEX® (1,800 mg, Week 1), 0.4% with the Week 2 injection, and 1.1% with subsequent injections. Grade 3 IRRs were seen in 0.8% of patients. No patients had Grade 4 IRRs.

infusion-second@1x.png
infusion-subsequent-1-0pc@1x.png

Adapted from DARZALEX® (daratumumab) EU SmPC[3]

Patients should receive appropriate pre-injection and post-injection medications to reduce the risk of IRRs (see treatment schedules).[3]

In clinical trials, no modification to rate or dose of DARZALEX® SC was required to manage IRRs. The median time to onset of IRRs following DARZALEX® injection was 3.2 hours (range: 0.15–83.00 hours). Most IRRs occurred on the day of treatment. Delayed IRRs have occurred in 1% of patients.[3]

The most common IRRs include:[3]

  • Nasal congestion
  • Cough
  • Throat irritation
  • Allergic rhinitis
  • Wheezing
  • Pyrexia
  • Chest pain
  • Pruritis
  • Chills
  • Vomiting
  • Nausea
  • Hypotension

Severe IRRs include:[3]

  • Bronchospasm
  • Hypoxia
  • Dyspnoea
  • Hypertension
  • Tachycardia

Administration

DARZALEX® solution for subcutaneous injection is for subcutanous use, and the recommended dose is 1800 mg administered over approximately 3–5 minutes.[3]

DARZALEX® should be administered by a healthcare professional, and the first dose should be administered in an environment where resuscitation facilities are available.[3]

Pre- and post-injection medications should be administered to reduce the risk of IRRs (see treatment schedules).[3]

Supplies you will need:[3]

  • Vial of DARZALEX® SC (1,800 mg/15 ml)
  • Syringe – 20 ml recommended
  • Transfer needle – 18G x 38 mm recommended
  • Alcohol swabs
  • Cotton ball or gauze pad
  • Adhesive bandage
  • Sharps bin

Either an injection needle or

  • 23G x 38 mm recommended

a winged/butterfly infusion set 

  • 23G x 19 mm recommended
Inspect the solution

1. Inspect the solution

  • Remove one DARZALEX® SC vial from the refrigerator and warm to room temperature 
  • Check that the DARZALEX® SC solution is clear to opalescent and colourless-to-yellow 
  • Do not use if opaque particles, discolouration or other foreign particles are present
Attach transfer needle and fill syringe

2. Attach transfer needle and fill syringe

  • Prepare the dosing syringe in controlled and validated aseptic conditions 
  • Attach the transfer needle to the syringe. Withdraw the full contents of the vial into the syringe using the transfer needle* 
  • Administer DARZALEX® SC within 4 hours of puncturing the vial or drawing the dose into the syringe 
  • If not used immediately, label the syringe with the date and time
Attach injection needle and set dose

3. Attach injection needle and set dose

  • Remove the transfer needle and attach the injection needle to the syringe 
  • Prime the syringe and set the dose to 15 ml
Choose the injection site

4. Choose the injection site

  • Choose a site on the abdomen, about 7,5 cm to the right or left of the navel 
  • Do not inject into skin that is tender, bruised, red, hard or has scars 
  • Wipe your chosen injection site with an alcohol swab and allow it to dry 
  • Rotate injection sites for each successive injection – note down which side was used each time


Insert needle

5. Insert needle

  • Pinch skin at the injection site. It is important to pinch enough skin to inject under the skin and not into the muscle 
  • Inject at a 45° angle 
  • Release pinched skin 
  • Check no blood vessel has been punctured


Inject dose

6. Inject dose

  • Press the plunger with a constant rate of delivery for about 3–5 minutes 
  • Try to limit needle and syringe movement during injection through a two-handed syringe grip If the patient feels pain, pause or slow down the rate of delivery. 
  • If the patient still feels pain, consider using a different injection site on the opposite side of the abdomen to deliver the remainder of the dose


After injection

7. After injection

  • Gently remove the needle 
  • Place a gauze pad or a cotton ball over the entrance site of the needle
Dispose of used syringe

8. Dispose of used syringe

  • Put the used syringe in a sharps disposal container right away after use


Check injection site

9. Check injection site

  • There may be a small amount of blood or liquid at the injection site. Hold pressure over skin with a cotton ball or gauze pad until any bleeding stops 
  • Do not rub the injection site. If needed, cover the injection site with a bandage


Inspect the solution

1. Inspect the solution

  • Remove one DARZALEX® SC vial from the refrigerator and warm to room temperature
  • Check that the DARZALEX® SC solution is clear to opalescent and colourless-to-yellow
  • Do not use if opaque particles, discolouration or other foreign particles are present
Choose the injection site

2. Choose the injection site

  • Choose a site on the abdomen, about 7,5 cm to the right or left of the navel 
  • Do not inject into skin that is tender, bruised, red, hard or has scars 
  • Wipe your chosen injection site with an alcohol swab and allow it to dry 
  • Rotate injection sites for each successive injection – note down which side was used each time
Prime infusion set

3. Prime infusion set

  • Flush the tubing of the infusion set with a small volume of saline solution or with the product itself 
  • Follow the instructions from your infusion set manufacturer
Attach transfer needle and fill syringe

4. Attach transfer needle and fill syringe

  • Prepare the dosing syringe in controlled and validated aseptic conditions 
  • Attach the transfer needle to the syringe. 
  • Withdraw the full contents of the vial into the syringe using the transfer needle* 
  • Administer DARZALEX® SC within 4 hours of puncturing the vial or drawing the dose into the syringe 

* Vials are overfilled to allow for infusion set administration


administer-sc-infusion-05@1x.png

5. Attach infusion set and set dose

  • Remove the transfer needle and attach the injection needle to the syringe 
  • Set the dose to 15 ml 
  • Follow the instructions from your infusion set manufacturer


Insert needle

6. Insert needle

  • Remove needle safety cap 
  • Pinch skin at the injection site. It is important to pinch enough skin to inject under the skin and not into the muscle 
  • Inject at a 45° angle 
  • Release pinched skin. If needed, secure site as per your institutional protocol (e.g., surgical tape)
Inject dose

7. Inject dose

  • Press the plunger with a constant rate of delivery for about 3–5 minutes (use phone/watch to track time) If the patient feels pain, pause or slow down the rate of delivery. 
  • If the patient still feels pain, consider using a different injection site on the opposite side of the abdomen to deliver the remainder of the dose 

Optional: After completion of administration, flush the syringe with saline to ensure the patient receives the full dose.


After injection

8. After injection

  • Remove the surgical tape, if used 
  • Gently remove the needle 
  • Place a gauze pad or a cotton ball over the entrance site of the needle 
  • Put the used syringe in a sharps disposal container right away after use


Check injection site

9. Check injection site

  • There may be a small amount of blood or liquid at the injection site. Hold pressure over skin with a cotton ball or gauze pad until any bleeding stops 
  • Do not rub the injection site. If needed, cover the injection site with a bandage

Unopened vials have a shelf life of 18 months. Do not use this medicine after the expiry date, which is stated on the carton after “EXP”.[3]

DARZALEX® SC should be stored in a refrigerator (2°C–8°C) and never frozen. It should be stored in the original package in order to protect from light.[3]

Before use, remove the vial from refrigerated storage (2°C–8°C) and equilibrate to ambient temperature (15°C–30°C).[3]

The unpunctured vial may be stored at ambient temperature and ambient light for a maximum of 24 hours in the original carton to protect from light. Keep out of direct sunlight. Do not shake.[3]

Once transferred from the vial into the syringe, DARZALEX® solution for injection can be stored for a maximum of 12 hours at ambient temperature (a 15 ºC-25ºC ) and ambient light.[3]

Quick downloads

SC Checklist beginning of treatment

Includes a first use checklist of Darzalex® SC.

Darzalex® SC Practical Guide

Includes DARZALEX® SC handling and administration info, pre and post-injection medications, and more

AL: amyloid light chain

ARR: administration-related reaction

CR: complete response

DVCd: DARZALEX® + Velcade® + cyclophosphamide + dexamethasone

IRR: infusion-related reaction

ISR: injection-site reactions

IV: intravenous

PO: oral

SC: subcutaneous

VCd: Velcade® + cyclophosphamide + dexamethasone

Titular da Autorização de Introdução no Mercado: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Bélgica.
Para mais informações deverá contactar o Representante do Titular da Autorização de Introdução no Mercado: Janssen-Cilag Farmacêutica, Lda.

Medicamento de receita médica restrita, de utilização reservada a certos meios especializados.

Antes de prescrever consulte o RCM completo.

RCM de Darzalex®, veja aqui

CP-287814 - March 2022
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