POLIVY

Indications

• Relapsed or refractory diffuse large B-cell lymphoma
• B-cell malignancies expressing CD79b

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric populations.

Adults: Refer to the BNF for specific dosing recommendations based on individual patient factors and treatment regimens.

Mechanism of action

Polatuzumab vedotin is an antibody-drug conjugate that binds specifically to CD79b on B-cells. Once bound, the conjugate is internalized, leading to the release of the cytotoxic agent monomethyl auristatin E (MMAE), which disrupts microtubule dynamics, ultimately inducing apoptosis in CD79b-expressing malignant B-cells.

Pharmacodynamics

The pharmacodynamics of polatuzumab vedotin involve the targeted delivery of the cytotoxic drug MMAE to B-cells, minimizing systemic exposure and toxicity. By specifically targeting CD79b, it can selectively induce cell death in malignant B-cells, while sparing normal cells, thus achieving an improved therapeutic index. The combination with other agents like bendamustine and rituximab has been shown to enhance antitumor activity compared to monotherapy.

Pharmacokinetics

Polatuzumab vedotin exhibits a half-life of approximately 5 to 7 days, with pharmacokinetics influenced by factors such as the patient's weight and the presence of other concurrent therapies. The drug is metabolized by proteolytic enzymes, and its clearance can be affected by concomitant medications that alter hepatic function or enzyme activity. The presence of CD79b-expressing cells in the circulation may also impact distribution and clearance.

Interactions

• cobicistat+polatuzumabvedotin: Unknown (increases exposure)
• idelalisib+polatuzumabvedotin: Unknown (increases exposure)
• clarithromycin+polatuzumabvedotin: Unknown (increases exposure)
• mitotane+polatuzumabvedotin: Unknown (decreases exposure)
• rifampicin+polatuzumabvedotin: Unknown (decreases exposure)

Indications

• Hodgkin lymphoma
• Anaplastic large cell lymphoma

Dosage

Children: Refer to the BNF for Children for guidance on dosing in paediatric patients, as this may vary based on age, weight, and clinical condition.

Adults: Refer to the BNF for specific dosing recommendations based on individual patient factors and treatment protocols.

Mechanism of action

Vedotin targets CD30, a cell surface protein that is overexpressed in certain malignancies, such as Hodgkin lymphoma and anaplastic large cell lymphoma. The monoclonal antibody component binds to CD30 on the surface of cancer cells, facilitating internalization of the drug. Once inside the cell, the cytotoxic agent is released, leading to disruption of microtubule function, ultimately resulting in cell cycle arrest and apoptosis.

Pharmacodynamics

Vedotin exhibits dose-dependent cytotoxicity against CD30-expressing cells. Its mechanism involves the inhibition of microtubule assembly, which is crucial for mitosis and cellular integrity. The compound's selectivity for CD30-positive cells helps to limit toxicity to normal cells, contributing to its therapeutic efficacy in targeted cancer treatment.

Pharmacokinetics

After intravenous administration, vedotin distributes widely in the body, with a volume of distribution that suggests extensive tissue binding. The drug is metabolized primarily by proteolytic cleavage, resulting in the release of the cytotoxic payload. Elimination occurs mainly through the hepatobiliary route, with a half-life that supports dosing intervals based on clinical needs. Monitoring may be required to assess clearance and potential accumulation in patients with altered liver function.

Pregnancy

There is limited data on the use of vedotin in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known if vedotin is excreted in human breast milk. Caution should be exercised when administering vedotin to a nursing woman.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. Protect from light.