inotuzumab

Inotuzumab ozogamicin, sold under the brand name Besponsa, is an antibody-drug conjugate designed to treat certain B-cell acute lymphoblastic leukemia (ALL). It consists of a humanized monoclonal antibody that targets CD22, linked to a cytotoxic agent, calicheamicin. The drug is indicated for adults with relapsed or refractory CD22-positive B-cell precursor ALL.

Mechanism of action: Inotuzumab ozogamicin binds to CD22 on the surface of malignant B cells and is internalized. Inside the cell, the calicheamicin payload is released, causing DNA double-strand breaks and cell death. This targeted delivery aims to spare non-CD22-expressing cells, though off-target effects and toxicities occur.

Administration and dosing: The medication is given by intravenous infusion in 21-day cycles. A common dosing regimen is 0.8 mg/m2 on day 1 followed by 0.5 mg/m2 on day 8, for up to two cycles, depending on response and tolerability. Treatment may be followed by hematopoietic stem cell transplantation in suitable patients, particularly after achieving remission.

Safety and warnings: Inotuzumab ozogamicin carries boxed warnings for hepatotoxicity, including fatal and life-threatening hepatobiliary veno-occlusive disease (VOD), and for mortality risk. The risk of VOD is higher in patients who proceed to transplantation or have underlying liver disease. Other adverse effects include cytopenias, infections, infusion-related reactions, mucosal symptoms, and electrolyte disturbances. Use in pregnancy poses risks to the fetus, and contraception is advised for patients of reproductive potential.

Pharmacology and availability: As an antibody-drug conjugate targeting CD22, inotuzumab ozogamicin is approved in several regions for adult relapsed or refractory CD22-positive B-cell precursor ALL and is marketed in the United States as Besponsa.