Overview
11 DESCRIPTION Polatuzumab vedotin-piiq is a CD79b-directed antibody and microtubule inhibitor conjugate. It consists of three components: 1) the humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for human CD79b; 2) the small molecule anti-mitotic agent MMAE; and 3) a protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB) that covalently...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate with activity against dividing B cells. The small molecule, MMAE, is an anti-mitotic agent covalently attached to the antibody via a cleavable linker. The monoclonal antibody binds to CD79b, a B-cell specific surface protein, which is a component of the B-cell receptor. Upon binding CD79b, polatuzumab vedotin-piiq is 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. 12.2 Pharmacodynamics Over polatuzumab vedotin-piiq dosages of 0.1 to 2.4 mg/kg (0.06 to 1.
Indications
- 1 INDICATIONS AND USAGE POLIVY is a CD79b-directed antibody and microtubule inhibitor conjugate indicated: in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of 2 or greater. ( 1.
Common Doses
- 1.8 mg
- 90 mg
- 375 mg
- 1.4 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dose of POLIVY is 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles. ( 2 ) Administer the initial POLIVY dose over 90 minutes. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated. ( 2 ) Premedicate with an antihistamine and antipyretic before POLIVY. ( 2 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.4 ) 2.1 Recommended Dosage Patients with Previously Untreated DLBCL, NOS or HGBL The recommended dosage of POLIVY is 1.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the label: Peripheral Neuropathy [see Warnings and Precautions (5.1) ] Infusion-Related Reactions [see Warnings and Precautions (5.2) ] Myelosuppression [see Warnings and Precautions (5.3) ] Serious and Opportunistic Infections [see Warnings and Precautions (5.4) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.5) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Concomitant use of strong CYP3A inhibitors or inducers has the potential to affect the exposure to unconjugated monomethyl auristatin E (MMAE). ( 7.1 ) 7.1 Effects of Other Drugs on POLIVY Strong CYP3A Inhibitors Concomitant use with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC [see Clinical Pharmacology (12.3) ] , which may increase POLIVY toxicities. Monitor patients for signs of toxicity. Strong CYP3A Inducers Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC [see Clinical Pharmacology (12.3) ] .