BESPONSA

What it is

BESPONSA is a CD22-directed antibody-drug conjugate consisting of a recombinant humanised immunoglobulin class G subtype 4 antibody specific for human CD22, a semisynthetic calicheamicin derivative that causes double-stranded DNA breaks, and an acid cleavable linker that covalently attaches the calicheamicin to the antibody. BESPONSA is supplied as a powder for injection, provided as 1 mg of white to off-white lyophilised cake or powder in a single dose vial for reconstitution and dilution.

Approved indications

— Treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia.

Dosing overview

BESPONSA is administered in 3- to 4-week cycles. For the first cycle, the recommended total dose is 1.8 mg/m² per cycle, administered as 3 divided doses on Days 1 (0.8 mg/m²), 8 (0.5 mg/m²), and 15 (0.5 mg/m²). For subsequent cycles, the recommended total dose is 1.5 mg/m² per cycle for patients who achieve a complete remission or complete remission with incomplete haematologic recovery, or 1.8 mg/m² per cycle for patients who do not achieve these responses, both administered as 3 divided doses on Days 1, 8, and 15. For patients proceeding to haematopoietic stem cell transplant, the recommended duration of treatment is 2 cycles; for patients not proceeding to transplant, a maximum of 6 cycles may be administered.

Key safety warnings

Hepatotoxicity, including fatal and life-threatening hepatic venoocclusive disease has occurred in patients treated with BESPONSA. In a randomised clinical study, hepatotoxicity including severe, life threatening, and sometimes fatal hepatic venoocclusive disease/sinusoidal obstruction syndrome was observed in 14% of patients during or following treatment or following haematopoietic stem cell transplant after completion of treatment. Due to the risk of venoocclusive disease/sinusoidal obstruction syndrome, especially after haematopoietic stem cell transplant, monitor closely for signs and symptoms including elevations in total bilirubin, hepatomegaly, rapid weight gain, and ascites. Monitor liver tests including alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase prior to and following each dose. An increased risk of post-haematopoietic stem cell transplant non-relapse mortality has been observed in patients treated with BESPONSA. A higher post-transplant non-relapse mortality rate was observed in patients receiving BESPONSA compared to investigator's choice of chemotherapy, and patients should be monitored closely for toxicities post-transplant, including signs and symptoms of infection and venoocclusive disease/sinusoidal obstruction syndrome. Neutropenia, thrombocytopenia, anaemia, leukopenia, febrile neutropenia, lymphopenia, and pancytopenia, some of which were life-threatening, were reported; infections including serious infections, some of which were life-threatening or fatal, were reported, with fatal infections including pneumonia, neutropenic sepsis, sepsis, septic shock, and pseudomonal sepsis. Monitor complete blood counts prior to each dose and monitor for signs and symptoms of infection, bleeding/haemorrhage, or other effects of myelosuppression during treatment. Infusion related reactions were reported and generally occurred in the first cycle shortly after the end of the infusion and resolved spontaneously or with medical management. Premedication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing.

Contraindications

Contraindications include hypersensitivity to inotuzumab ozogamicin or to any of the excipients, patients who have experienced prior confirmed severe or ongoing venoocclusive liver disease/sinusoidal obstruction syndrome, and patients with serious ongoing hepatic disease such as cirrhosis, nodular regenerative hyperplasia, or active hepatitis.

PBS listing

BESPONSA powder for intravenous infusion 1 mg is listed on the PBS with authority required restriction at an ex-manufacturer price of A$12,453.78.

Regulatory history

BESPONSA inotuzumab ozogamicin 1 mg powder for injection was first registered on the ARTG on 17 May 2018. In November 2018, the PBAC recommended BESPONSA as a new listing for relapsed or refractory CD22 positive B-cell precursor acute lymphoblastic leukaemia under authority required restrictions as part of special arrangements under Section 100 for efficient funding of chemotherapy. BESPONSA is subject to additional monitoring in Australia to allow quick identification of new safety information.