Polatuzumab
Introduction to Polatuzumab
Polatuzumab vedotin (trade name: Polivy) is an antibody-drug conjugate (ADC) used in the treatment of certain types of lymphoma. It was developed by Genentech, a subsidiary of Roche, and received FDA approval in 2019 for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in combination with bendamustine and rituximab.
Polatuzumab consists of three components:
- A humanized monoclonal antibody targeting CD79b, a protein expressed on B cells
- A protease-cleavable linker
- Monomethyl auristatin E (MMAE), a potent microtubule-disrupting agent
Mechanism of Action
Polatuzumab vedotin works through a targeted approach:
- Binding: The antibody portion of polatuzumab binds specifically to CD79b on B cells, including malignant B cells in lymphomas.
- Internalization: Upon binding, the ADC is internalized into the cell.
- Release of cytotoxic agent: Inside the cell, lysosomal enzymes cleave the linker, releasing MMAE.
- Cell death: MMAE disrupts the microtubule network, leading to cell cycle arrest and apoptosis of the dividing cells.
This mechanism allows for targeted delivery of the cytotoxic agent to B cells, potentially reducing off-target effects compared to traditional chemotherapy.
Indications
Polatuzumab vedotin is primarily indicated for:
- Adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least two prior therapies
- Used in combination with bendamustine and rituximab
While initially approved for adult patients, ongoing clinical trials are exploring its potential use in pediatric populations with relapsed or refractory B-cell non-Hodgkin lymphomas.
Administration
Polatuzumab vedotin is administered as an intravenous infusion. The typical dosing regimen is:
- 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles
- Given in combination with bendamustine and rituximab
- Premedication with an antihistamine and antipyretic is recommended
The first infusion should be administered over 90 minutes. If well-tolerated, subsequent infusions may be administered over 30 minutes.
Adverse Effects
Common adverse effects of polatuzumab vedotin include:
- Neutropenia and febrile neutropenia
- Thrombocytopenia
- Anemia
- Peripheral neuropathy
- Fatigue
- Diarrhea
- Fever
- Decreased appetite
- Pneumonia
Serious adverse reactions reported in ≥5% of patients included pneumonia, sepsis, and febrile neutropenia. Peripheral neuropathy is a significant concern and may be cumulative, requiring dose modification or discontinuation.
Monitoring
Patients receiving polatuzumab vedotin should be closely monitored for:
- Complete blood counts: Monitor for neutropenia, thrombocytopenia, and anemia
- Peripheral neuropathy: Assess for symptoms before each dose and consider dose modification if neuropathy worsens
- Infusion-related reactions: Monitor during infusion and for at least 90 minutes following completion of the first infusion
- Tumor lysis syndrome: Patients with high tumor burden may be at increased risk
- Hepatotoxicity: Monitor liver enzymes and bilirubin levels
- Progressive multifocal leukoencephalopathy (PML): Monitor for new or worsening neurological, cognitive, or behavioral signs or symptoms
