Polivy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami Ardakani
Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
Black Box Warning
|
Peripheral Neuropathy
See full prescribing information for complete Boxed Warning.
POLIVY can cause peripheral neuropathy, including severe cases. Peripheral neuropathy occurs as early as the first cycle of treatment and is a cumulative effect. POLIVY may exacerbate pre-existing peripheral neuropathy.
|
Overview
Polivy is a HUMAN PRESCRIPTION DRUG LABEL that is FDA approved for the treatment of POLIVY is a CD79b-directed antibody and microtubule inhibitor conjugate indicated: 1. 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. 2. in combination with bendamustine and a rituximab product for the treatment of adult patients with relapsed or refractory DLBCL, NOS, after at least two prior therapies.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Peripheral Neuropathy Infusion-Related Reactions Myelosuppression Serious and Opportunistic Infections Progressive Multifocal Leukoencephalopathy Tumor Lysis Syndrome Hepatotoxicity.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Patients with Previously Untreated DLBCL, NOS or HGBL
The recommended dosage of POLIVY is 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone. Administer POLIVY, cyclophosphamide, doxorubicin, and a rituximab product in any order on Day 1 after the administration of prednisone. Prednisone is administered on Days 1–5 of each cycle.
Patients with Relapsed or Refractory DLBCL, NOS
The recommended dosage of POLIVY is 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles in combination with bendamustine and a rituximab product. Administer POLIVY, bendamustine, and a rituximab product in any order on Day 1 of each cycle. The recommended dose of bendamustine is 90 mg/m2/day on Days 1 and 2 when administered with POLIVY and a rituximab product. The recommended dose of rituximab product is 375 mg/m2 intravenously on Day 1 of each cycle.
For All Indicated Patients
If not already premedicated, administer an antihistamine and antipyretic at least 30 minutes prior to POLIVY.
If a planned dose of POLIVY is missed, administer as soon as possible. Adjust the schedule of administration to maintain a 21-day interval between doses.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Polivy FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
There is limited information regarding Polivy Contraindications in the drug label.
Warnings
|
Peripheral Neuropathy
See full prescribing information for complete Boxed Warning.
POLIVY can cause peripheral neuropathy, including severe cases. Peripheral neuropathy occurs as early as the first cycle of treatment and is a cumulative effect. POLIVY may exacerbate pre-existing peripheral neuropathy.
|
Peripheral Neuropathy
Infusion-Related Reactions Myelosuppression Serious and Opportunistic Infections Progressive Multifocal Leukoencephalopathy (PML) Tumor Lysis Syndrome Hepatotoxicity Embryo-Fetal Toxicity
Adverse Reactions
Clinical Trials Experience
Peripheral Neuropathy Infusion-Related Reactions Myelosuppression Serious and Opportunistic Infections Progressive Multifocal Leukoencephalopathy Tumor Lysis Syndrome Hepatotoxicity
Postmarketing Experience
There is limited information regarding Polivy Postmarketing Experience in the drug label.
Drug Interactions
Concomitant use with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase POLIVY toxicities. Monitor patients for signs of toxicity.
Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): ased on findings from animal studies and its mechanism of action, POLIVY can cause fetal harm. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of the small molecule component of POLIVY, MMAE, to pregnant rats during organogenesis at exposures below the clinical exposure at the recommended dose of 1.8 mg/kg POLIVY every 21 days resulted in embryo-fetal mortality and structural abnormalities. Advise a pregnant woman of the potential risks to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Polivy in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Polivy during labor and delivery.
Nursing Mothers
There is no information regarding the presence of polatuzumab vedotin-piiq in human milk, the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with POLIVY and for 2 months after the last dose.
Pediatric Use
Safety and effectiveness of POLIVY have not been established in pediatric patients.
Geriatic Use
Among 435 patients treated with POLIVY plus R-CHP in POLARIX, 227 (52%) were ≥65 years of age. No overall differences in safety or efficacy were observed between patients aged ≥65 years and younger patients.
Among 173 patients treated with POLIVY plus BR in Study GO29365, 95 (55%) were ≥65 years of age. Patients aged ≥65 had a numerically higher incidence of serious adverse reactions (64%) than patients aged <65 (53%). This study did not include sufficient numbers of patients to determine whether efficacy differed in patients aged ≥65 and younger patients.
Gender
There is no FDA guidance on the use of Polivy with respect to specific gender populations.
Race
There is no FDA guidance on the use of Polivy with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Polivy in patients with renal impairment.
Hepatic Impairment
Avoid the administration of POLIVY in patients with moderate or severe hepatic impairment (total bilirubin greater than 1.5 × ULN and any AST). Patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions. POLIVY has not been studied in patients with moderate or severe hepatic impairment.
No adjustment in the starting dose is required when administering POLIVY to patients with mild hepatic impairment (total bilirubin 1 to 1.5 × ULN or AST greater than ULN).
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Polivy in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Polivy in patients who are immunocompromised.
Administration and Monitoring
Administration
Reconstitute and further dilute POLIVY prior to intravenous infusion.
POLIVY is a hazardous drug. Follow applicable special handling and disposal procedures.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Administer POLIVY as an intravenous infusion only. Administer the initial dose of POLIVY over 90 minutes. Monitor patients for infusion-related reactions during the infusion and for a minimum of 90 minutes following completion of the initial dose. If the previous 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 must be administered using a dedicated infusion line equipped with a sterile, non-pyrogenic, low-protein-binding in-line or add-on filter (0.2- or 0.22-micron pore size) and a catheter. Do not mix POLIVY with or administer as an infusion with other drugs.
Monitoring
There is limited information regarding Polivy Monitoring in the drug label.
IV Compatibility
Administer POLIVY as an intravenous infusion only.
Overdosage
There is limited information regarding Polivy overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Polivy Pharmacology in the drug label.
Mechanism of Action
olatuzumab 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.
Structure
There is limited information regarding Polivy Structure in the drug label.
Pharmacodynamics
Over polatuzumab vedotin-piiq dosages of 0.1 to 2.4 mg/kg (0.06 to 1.33 times the approved recommended dosage), higher exposures (AUC and Cmax) of antibody-conjugated MMAE (acMMAE) and unconjugated MMAE were associated with higher incidence of some adverse reactions (including ≥Grade 3 thrombocytopenia and ≥Grade 3 anemia). Higher exposure (AUC and Cmax) of unconjugated MMAE was associated with higher incidence of ≥Grade 2 peripheral neuropathy. Lower acMMAE exposure (AUC) was associated with lower efficacy in patients with relapsed or refractory DLBCL.
Cardiac Electrophysiology
Polatuzumab vedotin-piiq did not prolong the mean QTc interval to any clinically relevant extent based on ECG data from two open-label studies in patients with previously treated B-cell malignancies at the recommended dosage.
Pharmacokinetics
The plasma exposure of acMMAE and unconjugated MMAE increased proportionally over a polatuzumab vedotin-piiq dose range from 0.1 to 2.4 mg/kg (0.06 to 1.33 times the approved recommended dosage). Cycle 3 acMMAE AUC were predicted to increase by approximately 30% over Cycle 1 AUC, and achieved more than 90% of the Cycle 6 AUC. Unconjugated MMAE plasma exposures were <3% of acMMAE exposures, and the AUC and Cmax were predicted to decrease after repeated every-3-week dosing.
Nonclinical Toxicology
Carcinogenicity studies in animals have not been performed with polatuzumab vedotin-piiq or MMAE.
MMAE was positive for genotoxicity in the in vivo rat bone marrow micronucleus study through an aneugenic mechanism. MMAE was not mutagenic in the bacterial reverse mutation (Ames) assay or the L5178Y mouse lymphoma forward mutation assay.
Fertility studies in animals have not been performed with polatuzumab vedotin-piiq or MMAE. However, results of repeat-dose toxicity indicate the potential for polatuzumab vedotin-piiq to impair female and male fertility. In the 4-week repeat-dose toxicity study in rats with weekly dosing of 2, 6, and 10 mg/kg, dose-dependent testicular seminiferous tubule degeneration with abnormal lumen contents in the epididymis was observed. Findings in the testes and epididymis did not reverse and correlated with decreased testes weight and gross findings of small and/or soft testes at recovery necropsy in males given doses ≥2 mg/kg (below the exposure at the recommended dose based on unconjugated MMAE AUC).
MMAE-containing ADCs have been associated with adverse ovarian effects when administered to sexually immature animals. Adverse effects included decrease in, or absence of, secondary and tertiary ovarian follicles after weekly administration to cynomolgus monkeys in studies of 4-week duration. These effects showed a trend towards recovery 6 weeks after the end of dosing; no changes were observed in primordial follicles.
Clinical Studies
The efficacy of POLIVY was evaluated in POLARIX (NCT03274492), a randomized double-blind, placebo-controlled, multicenter trial in patients with previously untreated large B-cell lymphoma. Eligible patients were aged 18–80 and had an International Prognostic Index (IPI) score of 2–5 and ECOG performance status of 0–2. The study excluded patients with transformed lymphoma, primary mediastinal large B-cell lymphoma, known CNS lymphoma, or Grade 2 or higher peripheral neuropathy.
Patients were randomized in a 1:1 ratio to receive POLIVY plus R-CHP or to receive R-CHOP for six 21-day cycles followed by two additional cycles of rituximab alone in both arms. Randomization was stratified by IPI score (2 vs 3–5), presence or absence of bulky disease (lesion ≥7.5 cm), and geographical region. Dosing in each treatment arm was as follows:
POLIVY + R-CHP arm: POLIVY 1.8 mg/kg intravenously, rituximab 375 mg/m2 intravenously, cyclophosphamide 750 mg/m2 intravenously, and doxorubicin 50 mg/m2 intravenously on Day 1 and prednisone 100 mg orally once daily on Days 1–5 for 6 cycles. Rituximab 375 mg/m2 was administered intravenously on Day 1 of cycles 7 and 8. R-CHOP arm: rituximab 375 mg/m2 intravenously, cyclophosphamide 750 mg/m2 intravenously, doxorubicin 50 mg/m2 intravenously, and vincristine 1.4 mg/m2 intravenously on Day 1 and prednisone 100 mg orally once daily on Days 1–5 for 6 cycles. Rituximab 375 mg/m2 was administered intravenously on Day 1 of cycles 7 and 8. Prophylaxis with granulocyte-colony stimulating factor (G-CSF) was mandated for both arms. Dosing in both treatment arms was preceded by premedication.
Of the 879 patients randomized (440 to POLIVY plus R-CHP, 439 to R-CHOP), the median age was 65 years (range 19 to 80 years), 54% were male, 54% were White, 19% were Asian, 1.8% were Black or African American, and 6% were Hispanic or Latino. In total, 38% had an IPI score of 2, 62% had an IPI score of 3–5, 89% had Stage 3 or 4 disease, and 44% had bulky disease. The majority of patients had DLBCL, NOS (84%; n = 740), 11% (n = 93) had HGBL with MYC and BCL2 and/or BCL6 rearrangements or HGBL, NOS, and 5% had other large B-cell lymphomas.
How Supplied
POLIVY (polatuzumab vedotin-piiq) for injection is a preservative-free, white to grayish-white lyophilized powder, which has a cake-like appearance. POLIVY is supplied as one 30 mg single-dose vial or one 140 mg single-dose vial
Storage
Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not use beyond the expiration date shown on the carton. Do not freeze. Do not shake.
Images
Drug Images
{{#ask: Page Name::Polivy |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Polivy |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Polivy Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Polivy interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Polivy Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Polivy Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.