Inotuzumab ozogamicin — Drug Monograph

Brand names: Besponsa

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of a CD22-directed monoclonal antibody linked to N-acetyl-gamma-calicheamicin, a potent DNA-binding cytotoxic agent. The antibody portion binds to CD22-expressing B-cells, after which the ADC is internalized into lysosomes. Once inside, the calicheamicin is released via hydrolysis, where it binds to the minor groove of DNA and induces double-strand DNA breaks. This sequence of events leads to cell cycle arrest and apoptotic cell death in malignant B-cells.

FDA Indications

• Treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults.

Common Side Effects

• Thrombocytopenia
• Neutropenia
• Anemia
• Leukopenia
• Infection
• Fatigue
• Hemorrhage
• Pyrexia
• Nausea
• Headache
• Increased transaminases
• Abdominal pain

Clinical Pearl

The risk of Veno-occlusive Disease (VOD) is the most critical management issue, especially for patients bridging to an allogeneic stem cell transplant. To minimize this risk, clinicians should avoid double-alkylator conditioning regimens and keep the number of inotuzumab cycles to a minimum (ideally ≤2) before transplant. Prophylaxis with ursodiol is often employed in clinical practice, though not explicitly required by the label.

Related Therapies & Mechanisms

• Gemtuzumab ozogamicin (Mylotarg) — Antibody-Drug Conjugate · Leukemia
• Pivekimab sunirine (DECNUPAZ) — Antibody-Drug Conjugate · Leukemia
• Belantamab mafodotin (Blenrep) — Antibody-Drug Conjugate
• Brentuximab Vedotin (Adcetris) — Antibody-Drug Conjugate