Polivy 30 mg/vial

Polivy 30 mg/vial | INDICATIONS AND USES

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). Polatuzumab Vedotin in combination with bendamustine and rituximab is indicated for the treatment of adult patients with diffuse large B-cell lymphoma who have received at least one prior therapy.

Polivy 30 mg/vial | PHARMACOLOGY

Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent anti-mitotic agent (monomethyl auristatin E, or MMAE) to B-cells, which results in the killing of malignant B-cells. The polatuzumab vedotin molecule consists of MMAE covalently attached to a humanized immunoglobulin G1 (IgG1) monoclonal antibody via a cleavable linker. The monoclonal antibody binds with high affinity and selectivity to CD79b, a cell surface component of the B-cell receptor. CD79b expression is restricted to normal cells within the B-cell lineage (with the exception of plasma cells) and malignant B-cells; it is expressed in >95% of DLBCL. Upon binding CD79b, polatuzumab vedotin is rapidly internalized and the linker is cleaved by lysosomal proteases to enable intracellular delivery of MMAE. MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis.

Polivy 30 mg/vial | DOSAGE & ADMINISTRATION

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.

Polivy 30 mg/vial | DRUG INTERACTIONS

No dedicated clinical drug-drug interaction studies with Polatuzumab vedotin in humans have been conducted.Drug interactions with co-medications that are CYP3A inhibitors, inducers or substratesBased on physiological-based pharmacokinetic (PBPK) model simulations of MMAE released from polatuzumab vedotin, strong CYP3A inhibitors (e.g., ketoconazole) may increase the area under the concentration-time curve (AUC) of unconjugated MMAE by 48%. Monitor patients receiving concomitant strong CYP3A inhibitors more closely for signs of toxicities. Strong CYP3A inducers (e.g., rifampin) may decrease the AUC of unconjugated MMAE by 49%.Unconjugated MMAE is not predicted to alter the AUC of concomitant drugs that are CYP3A substrates (e.g., midazolam).Drug interactions of rituximab bendamustine, cyclophosphamide, and doxorubicin in combination with polatuzumab vedotin.The pharmacokinetics (PK) of rituximab bendamustine, cyclophosphamide, and doxorubicin are not affected by co-administration with Polatuzumab vedotin. Concomitant rituximab is associated with increased antibody conjugated MMAE (acMMAE) plasma AUC by 24% and decreased unconjugated MMAE plasma AUC by 37%, based on population PK analysis. The plasma AUC of acMMAE and unconjugated MMAE for Polatuzumab vedotin plus R-CHP are in line with other studies of Polatuzumab vedotin. No dose adjustment is required. Bendamustine does not affect acMMAE and unconjugated MMAE plasma AUC

Polivy 30 mg/vial | USE DURING PREGNANCY AND LACTATION

Pregnancy: Polatuzumab Vedotin is not recommended during pregnancy unless the potential benefit for the mother outweighs the potential risk to the fetus. Polatuzumab Vedotin can cause fetal harm based on the animal studies and the drug’s mechanism of action.Lactation: It is not known whether polatuzumab vedotin is excreted in human breast milk. No studies have been conducted to assess the impact of Polivy on milk production or its presence in breast milk. Since many drugs are excreted in human milk and because of the potential for serious adverse reactions in breastfeeding infants due to Polivy, women should discontinue breastfeeding during Polivy treatment and for at least 3 months after the last dose.

Polivy 30 mg/vial | USE IN SPECIAL POPULATIONS

Pediatric use: The safety and efficacy of Polivy in children and adolescents (<18 years) has not been established.Geriatric use: No dose adjustment of Polivy is required in patients ≥65 years of age.Renal Impairment: No dose adjustment of Polivy is required in patients with creatinine clearance (CrCL) ≥30 ml/min.

Polivy 30 mg/vial | STORAGE CONDITIONS

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