General Information

Besponsa (inotuzumab ozogamicin) is a CD22-directed antibody-drug conjugate (ADC).

Besponsa is specifically indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

Besponsa is supplied as a solution for intravenous injection. The recommended dose schedule is as follows:

For the first cycle: the recommended total dose of Besponsa for all patients is 1.8 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Cycle 1 is 3 weeks in duration, but may be extended to 4 weeks if the patient achieves a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), and/or to allow recovery from toxicity.

For subsequent cycles: In patients who achieve a CR or CRi, the recommended total dose of Besponsa is 1.5 mg/m2per cycle, administered as 3 divided doses on Day 1 (0.5 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration. OR In patients who do not achieve a CR or CRi, the recommended total dose of Besponsa is 1.8 mg/m2 per cycle given as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration. Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment.

For patients proceeding to hematopoietic stem cell transplant (HSCT), the recommended duration of treatment with Besponsa is 2 cycles. A third cycle may be considered for those patients who do not achieve CR or CRi and minimal residual disease (MRD) negativity after 2 cycles.

For patients not proceeding to HSCT, additional cycles of treatment, up to a maximum of 6 cycles, may be administered.

Please see drug label for specific dose modifications based on toxicities.

Clinical Results

FDA Approvals

The FDA approval of Besponsa was based on a randomized trial of 326 patients with relapsed or refractory B-cell ALL who had received one or two prior treatments. Patients were randomized to receive treatment with Besponsa or an alternative chemotherapy regimen. The trial measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment (complete remission or CR). Of the 218 evaluated patients, 35.8 percent who received Besponsa experienced CR for a median 8.0 months; of the patients who received alternative chemotherapy, 17.4 percent experienced CR for a median 4.9 months.

Side Effects

Adverse effects associated with the use of Besponsa may include, but are not limited to, the following:

thrombocytopenia

neutropenia

infection

anemia

leukopenia

fatigue

hemorrhage

pyrexia

nausea

headache

febrile neutropenia

transaminases increased

abdominal pain

gamma-glutamyltransferase increased

hyperbilirubinemia

The Besponsa drug label includes a boxed warning that severe liver damage (hepatotoxicity), including blockage of veins in the liver (veno-occlusive disease [VOD] or sinusoidal obstruction syndrome), occurred in some patients who took Besponsa.

Mechanism of Action

Besponsa (inotuzumab ozogamicin) is a CD22-directed antibody-drug conjugate (ADC). Inotuzumab recognizes human CD22. The small molecule, N-acetyl-gamma-calicheamicin, is a cytotoxic agent that is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of inotuzumab ozogamicin is due to the binding of the ADC to CD22-expressing tumor cells, followed by internalization of the ADC-CD22 complex, and the intracellular release of N-acetyl-gamma-calicheamicin dimethylhydrazide via hydrolytic cleavage of the linker. Activation of N-acetyl-gamma-calicheamicin dimethylhydrazide induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death.