Polatuzumab Vedotin, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP), is indicated for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL). It is also indicated in combination with bendamustine and rituximab for the treatment of adult patients with diffuse large B-cell lymphoma who have received at least one prior therapy.

Polatuzumab Vedotin is a CD79b-targeted antibody-drug conjugate that selectively delivers a strong anti-mitotic agent called monomethyl auristatin E (MMAE) to B-cells, resulting in the destruction of malignant B-cells. The molecule consists of MMAE covalently linked to a humanized immunoglobulin G1 (IgG1) monoclonal antibody through a cleavable linker. This monoclonal antibody binds strongly and selectively to CD79b, a cell surface component of the B-cell receptor. CD79b is mainly expressed on normal B-cell lineage cells (except plasma cells) and malignant B-cells, and it is found in more than 95% of DLBCL cases. After binding to CD79b, Polatuzumab Vedotin is rapidly internalized into the cell, where the linker is broken down by lysosomal proteases, releasing MMAE inside the cell. MMAE then binds to microtubules, blocks cell division, and induces apoptosis, leading to the death of dividing cancer cells.

Diffuse large B-cell lymphoma

Previously untreated patients: The recommended dose of Polivy is 1.8 mg/kg given as an intravenous infusion every 21 days for 6 cycles in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP). Polivy, rituximab, cyclophosphamide, and doxorubicin can be administered in any order on Day 1 after the administration of prednisone. Prednisone is administered on Days 1–5 of each cycle. Cycles 7 and 8 consist of rituximab as monotherapy.

Relapsed or refractory patients: The recommended dose of Polivy is 1.8 mg/kg given as an intravenous infusion every 21 days in combination with bendamustine and rituximab for 6 cycles. Polivy, bendamustine, and rituximab can be administered in any order on Day 1 of each cycle. The recommended dose of bendamustine is 90 mg/m2/day on Day 1 and 2 when administered with Polivy and rituximab.

Previously untreated and relapsed or refractory patients: If not already premedicated, administer premedication with an antihistamine and anti-pyretic to patients prior to administration of Polivy. The initial dose of Polivy should be administered as a 90-minute intravenous infusion. Patients should be monitored for infusion-related reactions during the infusion and for at least 90 minutes following completion of the initial dose. If the prior infusion was well tolerated, the subsequent dose of Polivy may be administered as a 30-minute infusion and patients should be monitored during the infusion and for at least 30 minutes after completion of the infusion.

No specific clinical drug-drug interaction studies have been conducted with Polatuzumab Vedotin in humans.

Based on physiologically based pharmacokinetic (PBPK) model simulations, strong CYP3A inhibitors such as ketoconazole may increase the exposure (AUC) of unconjugated MMAE by about 48%. Patients receiving strong CYP3A inhibitors together with Polatuzumab Vedotin should be monitored closely for signs of toxicity.

Strong CYP3A inducers such as rifampin may decrease the AUC of unconjugated MMAE by about 49%. Unconjugated MMAE is not expected to significantly affect the exposure of drugs that are CYP3A substrates, such as midazolam.

The pharmacokinetics of rituximab, bendamustine, cyclophosphamide, and doxorubicin are not significantly affected when used with Polatuzumab Vedotin. Concomitant rituximab may increase antibody-conjugated MMAE plasma AUC by 24% and decrease unconjugated MMAE plasma AUC by 37%, but no dose adjustment is required. Bendamustine does not significantly affect MMAE exposure.

Polivy is contraindicated in patients with known hypersensitivity to Polatuzumab Vedotin or any of its excipients.

Pregnancy: Polatuzumab Vedotin is not recommended during pregnancy unless the potential benefit to the mother outweighs the possible risk to the fetus. Based on animal studies and its mechanism of action, it may cause fetal harm.

Lactation: It is not known whether Polatuzumab Vedotin is excreted in human breast milk. Due to the possibility of serious adverse reactions in breastfed infants, breastfeeding should be discontinued during treatment and for at least 3 months after the last dose.

Pediatric use: The safety and effectiveness of Polivy in children and adolescents below 18 years of age have not been established.

Geriatric use: No dose adjustment is required for patients aged 65 years and older.

Renal impairment: No dose adjustment is needed for patients with creatinine clearance (CrCL) ≥30 ml/min.

Store unopened vials at 2°C to 8°C. Keep the vial in the original outer carton to protect from light. Do not freeze. Do not shake.