DARZALEX

What it is

Daratumumab is an immunoglobulin G1 kappa (IgG1κ) human monoclonal antibody against CD38 antigen. DARZALEX SC is available as a colourless to yellow, clear to opalescent, preservative-free solution for subcutaneous administration. Each single-use vial contains 1800 mg of daratumumab (120 mg/mL).

Approved indications

— Newly diagnosed multiple myeloma in patients eligible for autologous stem cell transplant, in combination with bortezomib, thalidomide, and dexamethasone, or bortezomib, lenalidomide, and dexamethasone followed by maintenance treatment with lenalidomide. — Newly diagnosed multiple myeloma in patients ineligible for autologous stem cell transplant, in combination with bortezomib, melphalan and prednisone, or lenalidomide and dexamethasone. — Relapsed or refractory multiple myeloma in patients who have received at least one prior therapy, in combination with bortezomib and dexamethasone, lenalidomide and dexamethasone, carfilzomib and dexamethasone, or pomalidomide and dexamethasone (after at least one prior therapy including lenalidomide and a proteasome inhibitor). — Relapsed or refractory multiple myeloma in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are refractory to both a proteasome inhibitor and an immunomodulatory agent, as monotherapy. — Light chain AL amyloidosis, in combination with bortezomib, cyclophosphamide and dexamethasone.

Dosing overview

For newly diagnosed multiple myeloma eligible for autologous stem cell transplant in combination with bortezomib, thalidomide and dexamethasone, the recommended dose is DARZALEX SC 1800 mg administered subcutaneously over approximately 3–5 minutes, given weekly for 8 weeks, then every two weeks for 4 weeks during induction, followed by every two weeks for 4 weeks during consolidation. For newly diagnosed multiple myeloma eligible for autologous stem cell transplant in combination with bortezomib, lenalidomide and dexamethasone, the recommended dose is DARZALEX SC 1800 mg administered subcutaneously over approximately 3–5 minutes, given weekly for 8 weeks, then every two weeks for 4 weeks during induction, followed by every two weeks for 4 weeks during consolidation, then every four weeks as maintenance until disease progression. For newly diagnosed multiple myeloma ineligible for autologous stem cell transplant in combination with bortezomib, melphalan and prednisone, the recommended dose is DARZALEX SC 1800 mg administered subcutaneously over approximately 3–5 minutes, given weekly for 6 weeks, then every three weeks for 16 weeks, then every four weeks until disease progression. For relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone, the recommended dose is DARZALEX SC 1800 mg administered subcutaneously over approximately 3–5 minutes, given weekly for 9 weeks, then every three weeks for 5 weeks, then every four weeks until disease progression. For relapsed or refractory multiple myeloma in combination with lenalidomide, pomalidomide or carfilzomib and dexamethasone, or as monotherapy, the recommended dose is DARZALEX SC 1800 mg administered subcutaneously over approximately 3–5 minutes, given weekly for 8 weeks, then every two weeks for 8 weeks, then every four weeks until disease progression. For AL amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone, the recommended dose is DARZALEX SC 1800 mg administered subcutaneously over approximately 3–5 minutes, given weekly for 8 weeks, then every two weeks for 8 weeks, then every four weeks until disease progression.

Key safety warnings

DARZALEX SC can cause severe and/or serious infusion-related reactions, including anaphylactic reactions. In clinical trials, approximately 8% of patients experienced an infusion-related reaction, with most occurring following the first injection and being Grade 1–2. Signs and symptoms may include respiratory symptoms such as nasal congestion, cough, throat irritation, allergic rhinitis and wheezing, as well as pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension and blurred vision. Severe reactions have included bronchospasm, hypoxia, dyspnoea, hypertension, tachycardia and ocular adverse events including choroidal effusion, acute myopia and acute angle closure glaucoma. If an anaphylactic reaction or life-threatening (Grade 4) reactions occur, institute appropriate emergency care and permanently discontinue DARZALEX SC. DARZALEX SC increases the incidence of neutropenia and thrombocytopenia. Complete blood cell counts should be monitored periodically during treatment as per clinical judgment but not less frequently than prescribing information for background therapies. In lower body weight patients (≤65 kg) receiving DARZALEX SC, higher rates of neutropenia were observed including an increase in Grade 3–4 neutropenia. No dose reduction of DARZALEX SC is recommended; consider supportive care with transfusions or growth factors. Hepatitis B virus (HBV) reactivation, in some cases fatal, has been reported in patients treated with daratumumab. HBV screening should be performed in all patients before initiation of treatment with DARZALEX SC. For patients with evidence of positive HBV serology, monitor for clinical and laboratory signs of HBV reactivation during and for at least six months following the end of DARZALEX SC treatment.

Contraindications

Patients with a history of severe hypersensitivity (for example anaphylactic reaction) to daratumumab, or to any of the excipients should not receive DARZALEX SC.

PBS listing

DARZALEX SC is listed on the PBS as a solution for subcutaneous injection containing daratumumab 1800 mg in 15 mL, with 16 items, authority required restriction, and an ex-manufacturer price of A$6659.77.

Regulatory history

DARZALEX SC daratumumab 1800 mg/15 mL solution for injection was first listed on the ARTG on 2020-09-08. In July 2020, the PBAC recommended DARZALEX for multiple myeloma as second-line treatment in combination with bortezomib and dexamethasone. In July 2021, the PBAC recommended it for relapsed and/or refractory multiple myeloma. In May 2022, the PBAC recommended DARZALEX SC in combination with cyclophosphamide, bortezomib and dexamethasone for newly diagnosed AL amyloidosis. In March 2025, the PBAC recommended DARZALEX for transplant ineligible, newly diagnosed multiple myeloma in combination with lenalidomide and dexamethasone.