BLINCYTO

What it is

Blincyto is blinatumomab, a powder for injection containing 38.5 micrograms per vial. It is a novel bispecific T-cell engaging antibody targeting CD3 and CD19. Blincyto is supplied as a lyophilised powder for injection with IV stabiliser solution.

Approved indications

— Relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. — Minimal residual disease positive B-cell precursor acute lymphoblastic leukaemia in patients in complete haematological remission. — B-cell precursor acute lymphoblastic leukaemia in the consolidation phase in combination with chemotherapy in patients with Philadelphia chromosome negative disease. — B-cell precursor acute lymphoblastic leukaemia in the consolidation phase in combination with a tyrosine kinase inhibitor in patients with Philadelphia chromosome positive disease, who are unable to receive chemotherapy.

Dosing overview

Blincyto is administered as a continuous intravenous infusion delivered at a constant flow rate using an infusion pump. A single cycle of treatment is 28 days of continuous infusion followed by a 14-day treatment-free interval. Patients weighing 45 kg or greater receive a fixed dose, and for patients less than 45 kg, the dose is calculated using the patient's body surface area. For relapsed or refractory B-cell precursor ALL in patients 45 kg or greater, the recommended dose is 9 micrograms per day for days 1–7 of cycle 1, then 28 micrograms per day for days 8–28, with a 14-day treatment-free interval for subsequent cycles. For minimal residual disease positive B-cell precursor ALL in patients 45 kg or greater, the recommended dose is 28 micrograms per day for days 1–28, with a 14-day treatment-free interval. For B-cell precursor ALL in the consolidation phase in patients 45 kg or greater, the recommended dose is 28 micrograms per day for days 1–28, with a 14-day treatment-free interval.

Key safety warnings

Cytokine release syndrome, which may be life-threatening or fatal, has occurred in patients receiving Blincyto. Serious adverse events that may be associated with cytokine release syndrome included pyrexia, asthenia, headache, hypotension, elevated total bilirubin, and nausea. In some cases, disseminated intravascular coagulation, capillary leak syndrome, and haemophagocytic lymphohistiocytosis or macrophage activation syndrome have been reported in the setting of cytokine release syndrome. Neurological toxicities, which may be severe, life-threatening, or fatal, have occurred in patients receiving Blincyto. Neurological events including immune effector cell-associated neurotoxicity syndrome have been observed, with the median time to the first event within the first two weeks of Blincyto treatment and the majority of events resolving. Grade 3 or higher neurological events included encephalopathy, seizures, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders, with some events reported with a fatal outcome. Reactivation of JC viral infection has occurred in patients receiving Blincyto. Patients with acute lymphoblastic leukaemia are immunocompromised and at increased risk for serious infections; serious infections including sepsis, pneumonia, bacteraemia, opportunistic infections, and catheter site infections have been observed in patients receiving Blincyto, some of which were life-threatening or fatal. Tumour lysis syndrome, which may be life-threatening or fatal, has been observed in patients receiving Blincyto, and appropriate prophylactic measures including hydration should be used for prevention. Neutropenia and febrile neutropenia, including life threatening cases, have been observed in patients receiving Blincyto, and laboratory parameters including white blood cell count and absolute neutrophil count should be monitored during infusion.

Contraindications

Blincyto is contraindicated in patients with known hypersensitivity to CHO-cell derived proteins, blinatumomab, or any of the excipients.

PBS listing

Blincyto 38.5 micrograms powder for intravenous infusion is listed on the PBS with authority required restriction at an ex-manufacturer price of A$2759.53.

Regulatory history

Blincyto was approved for the treatment of adults with Philadelphia chromosome-negative relapsed or refractory B-precursor acute lymphoblastic leukaemia on 30 October 2015, with the product entering the ARTG on 9 November 2015. In July 2016, the Pharmaceutical Benefits Scheme Advisory Committee recommended Blincyto for listing for the treatment of relapsed or refractory Philadelphia chromosome negative B-precursor acute lymphocytic leukaemia, initially with authority required listing and a managed entry scheme to manage financial burden. In November 2016, the recommendation was revised with a removal of the managed entry scheme. In May 2019, the listing was extended to include patients with Philadelphia chromosome positive B-cell precursor acute lymphoblastic leukaemia. In July 2019, the listing was extended to minimal residual disease positive B-cell precursor acute lymphoblastic leukaemia in patients in complete haematological remission following induction chemotherapy. In November 2024, the Pharmaceutical Benefits Scheme Advisory Committee recommended listing for measurable residual disease-negative B-cell precursor acute lymphoblastic leukaemia.