QARZIBA

What it is

QARZIBA contains dinutuximab beta, a mouse-human chimeric monoclonal IgG1 antibody produced in a mammalian cell line by recombinant DNA technology. It is presented as a colourless to slightly yellow liquid concentrate for solution for infusion. Each vial contains 20 mg dinutuximab beta in 4.5 mL, with a concentration of 4.5 mg per mL.

Approved indications

— High-risk neuroblastoma in patients who have previously received induction chemotherapy and achieved at least a partial response.

Dosing overview

Treatment with QARZIBA consists of 5 consecutive courses, each course comprising 35 days, with the individual dose determined based on body surface area for a total of 100 mg/m² per course. There are two possible administration schedules: continuous infusion given over the first 10 days of each course at 10 mg/m²/day, or divided daily infusions administered as an 8-hour infusion once per day for the first 5 days at 20 mg/m²/day. Administration by the continuous infusion method may reduce likelihood or severity of adverse effects. Prior to starting each treatment course, clinical parameters must be evaluated and treatment should be delayed until pulse oximetry is greater than 94% on room air, absolute neutrophil count is at least 500/μL, platelet count is at least 20,000/μL, haemoglobin is greater than 8.0 g/dL, alanine aminotransferase and aspartate aminotransferase are less than 5 times upper limit of normal, and creatinine clearance or glomerular filtration rate is greater than 60 mL/min/1.73 m².

Key safety warnings

Neuropathic pain usually occurs at the beginning of treatment and premedication with analgesics, including intravenous opioids, prior to each infusion is required, with triple therapy including nonopioid analgesics, gabapentin and opioids recommended for pain treatment. Severe infusion-related reactions, including cytokine release syndrome, anaphylactic and hypersensitivity reactions, may occur despite the use of premedication, and occurrence of a severe infusion related reaction requires immediate discontinuation of QARZIBA therapy and may necessitate emergency treatment. Antihistamine premedication such as diphenhydramine should be administered by intravenous injection approximately 20 minutes before starting each infusion, with antihistamine administration repeated every 4 to 6 hours as required during infusion. Capillary leak syndrome is characterised by loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space, usually developing within hours after initiation of treatment with clinical symptoms such as hypotension and tachycardia occurring after 2 to 12 hours, requiring careful monitoring of circulatory and respiratory function. Eye disorders may occur as dinutuximab beta binds to optic nerve cells, and in case of any eye problems, patients should be referred promptly to an ophthalmology specialist. Central neurotoxicity has been reported following treatment with QARZIBA; if central neurotoxicity occurs the infusion should be interrupted immediately and the patient treated symptomatically, with other influencing factors such as active infection and neurotoxic concomitant medications ruled out. Atypical haemolytic uraemic syndrome has been reported in patients who received dinutuximab beta, in some cases with fatal outcome, and if diagnosed, prompt treatment is required and QARZIBA should be permanently discontinued.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in the product information. Acute grade 3 or 4, or extensive chronic graft-versus-host disease.

PBS listing

Information regarding PBS listing is not contained in the provided source documents.

Regulatory history

In November 2017, the PBAC recommended QARZIBA as a new medicine for the treatment of high-risk neuroblastoma. QARZIBA was approved by the TGA on 17 March 2020 for the treatment of high-risk neuroblastoma in patients who have received induction chemotherapy and achieved at least a partial response. QARZIBA dinutuximab beta 4.5 mg/mL concentrate for solution for infusion was first listed on the ARTG on 2 April 2020.