Class: Antibody-drug conjugate (ADC)
Mechanism of Action:
- Monoclonal antibody targeting CD22 on B cells linked to calicheamicin (a potent cytotoxic agent)
- Binds CD22 → internalization → release of calicheamicin → DNA double-strand breaks → apoptosis
Indications
- Relapsed/refractory B-cell precursor Acute Lymphoblastic Leukemia (ALL) in adults
Dosing
- IV infusion on days 1, 8, and 15 of a 28-day cycle
- Dose based on body surface area (usually ~1.8 mg/m²/cycle divided over 3 doses)
- Dose adjustments required for hepatic impairment
Key Adverse Effects
- Hepatotoxicity, including veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) — especially post-HSCT
- Myelosuppression: neutropenia, thrombocytopenia, anemia
- Infusion-related reactions
- QT prolongation
- Infections (due to neutropenia)
- Tumor lysis syndrome (TLS)
Monitoring
- Liver function tests (baseline and frequent during therapy)
- CBC regularly for cytopenias
- Signs/symptoms of VOD (weight gain, hepatomegaly, jaundice)
- ECG if at risk for QT prolongation
- Electrolytes and TLS labs during treatment initiation
Supportive Care
- Avoid or delay HSCT in patients with active VOD
- Use prophylaxis and monitoring for TLS
- Manage infusion reactions with premedication (antihistamines, corticosteroids)
- Infection prophylaxis as indicated
Other Important Notes
- Effective in patients who failed prior therapies, including chemotherapy and TKIs
- CD22 expression required on leukemic blasts
- Higher VOD risk when followed by HSCT or in patients with prior liver disease
- Consider dose modifications in hepatic impairment