Inotuzumab ozogamicin

Inotuzumab ozogamicin (Besponsa) is a targeted antibody-drug conjugate used primarily for adults with relapsed or refractory B-cell Acute Lymphoblastic Leukemia (ALL).

Key Characteristics

  • Mechanism of Action: It consists of a fully humanized monoclonal antibody targeting CD22 (found on B-cells) conjugated to calicheamicin, a potent cytotoxic antibiotic agent. Once it binds to CD22, it is internalized by the cell, where the calicheamicin is released to cause DNA damage and cell death.
  • Clinical Efficacy: In the phase 3 INO-VATE trial, it demonstrated significantly higher complete remission rates (73.8% vs. 30.9%) and higher rates of MRD negativity compared to standard intensive chemotherapy.
  • Administration: It is typically administered as an intermittent infusion on days 1, 8, and 15 of a 21-day cycle.

Safety and Warnings

Inotuzumab carries two Black Box Warnings:

  1. Hepatotoxicity: Specifically veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, which occurred in 14% of patients in clinical trials.
  2. Post-Transplant Mortality: A higher rate of non-relapse mortality in patients who proceed to a hematopoietic stem cell transplant (HSCT) after receiving this drug.

Because of these risks, it is recommended to limit the number of cycles to the minimum necessary if a patient is heading toward a transplant.

Key Adverse Effects

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
Synonyms
Inotuzumab, Besponsa
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