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

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