Skip to Content

Polivy

Generic Name: Polatuzumab Vedotin-piiq
Class: Antineoplastic Agents

Medically reviewed by Drugs.com. Last updated on Jul 1, 2019.

Introduction

Polatuzumab vedotin-piiq is an antineoplastic agent.

Uses for Polivy

Polatuzumab vedotin-piiq has the following uses:

Polatuzumab vedotin-piiq is a CD79b-directed antibody–drug conjugate indicated in combination with bendamustine and a rituximab product for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies.1

Accelerated approval was granted for this indication based on complete response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1

Polivy Dosage and Administration

General

Polatuzumab vedotin-piiq is available in the following dosage form(s) and strength(s):

For injection: 140 mg of polatuzumab vedotin-piiq as a lyophilized powder in a single-dose vial.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration
  • The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.1

  • Premedicate with an antihistamine and antipyretic before polatuzumab vedotin-piiq.1

  • See Full Prescribing Information for instructions on preparation and administration.1

  • Consult manufacturer’s labeling for recommended dosage modifications for toxicity.1

Cautions for Polivy

Contraindications

None.1

Warnings/Precautions

Peripheral Neuropathy

Polatuzumab vedotin-piiq can cause peripheral neuropathy, including severe cases. Peripheral neuropathy occurs as early as the first cycle of treatment and is a cumulative effect. Polatuzumab vedotin-piiq may exacerbate pre-existing peripheral neuropathy.1

In Study GO29365, of 173 patients treated with polatuzumab vedotin-piiq, 40% reported new or worsening peripheral neuropathy, with a median time to onset of 2.1 months. The peripheral neuropathy was Grade 1 in 26% of cases, Grade 2 in 12%, and Grade 3 in 2.3%. Peripheral neuropathy resulted in polatuzumab vedotin-piiq dose reduction in 2.9% of treated patients, dose delay in 1.2%, and permanent discontinuation in 2.9%. Sixty-five percent of patients reported improvement or resolution of peripheral neuropathy after a median of 1 month, and 48% reported complete resolution.1

The peripheral neuropathy is predominantly sensory; however, motor and sensorimotor peripheral neuropathy also occur. Monitor for symptoms of peripheral neuropathy such as hypoesthesia, hyperesthesia, paresthesia, dysesthesia, neuropathic pain, burning sensation, weakness, or gait disturbance. Patients experiencing new or worsening peripheral neuropathy may require a delay, dose reduction, or discontinuation of polatuzumab vedotin-piiq.1

Infusion-related Reactions

Polatuzumab vedotin-piiq can cause infusion-related reactions, including severe cases. Delayed infusion-related reactions as late as 24 hours after receiving polatuzumab vedotin-piiq have occurred. With premedication, 7% of patients (12/173) in Study GO29365 reported infusion-related reactions after the administration of polatuzumab vedotin-piiq. The reactions were Grade 1 in 67%, Grade 2 in 25%, and Grade 3 in 8%. Symptoms included fever, chills, flushing, dyspnea, hypotension, and urticaria.1

Administer an antihistamine and antipyretic prior to the administration of polatuzumab vedotin-piiq, and monitor patients closely throughout the infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management.1

Myelosuppression

Treatment with polatuzumab vedotin-piiq can cause serious or severe myelosuppression including neutropenia, thrombocytopenia, and anemia. In patients treated with polatuzumab vedotin-piiq in combination with bendamustine and a rituximab product (n = 45), 42% received primary prophylaxis with a granulocyte colony stimulating factor. Grade 3 or higher hematologic adverse reactions included neutropenia (42%), thrombocytopenia (40%), anemia (24%), lymphopenia (13%), and febrile neutropenia (11%). Grade 4 hematologic adverse reactions included neutropenia (24%), thrombocytopenia (16%), lymphopenia (9%), and febrile neutropenia (4.4%). Cytopenias were the most common reason for treatment discontinuation (18% of all patients).1

Monitor complete blood counts throughout treatment. Cytopenias may require a delay, dose reduction, or discontinuation of polatuzumab vedotin-piiq. Consider prophylactic granulocyte colony stimulating factor administration.1

Serious and Opportunistic Infections

Fatal and/or serious infections, including opportunistic infections such as sepsis, pneumonia (including Pneumocystis jiroveci and other fungal pneumonia), herpesvirus infection, and cytomegalovirus infection have occurred in patients treated with polatuzumab vedotin-piiq.1

Grade 3 or higher infections occurred in 32% (55/173) of patients treated with polatuzumab vedotin-piiq. Infection-related deaths were reported in 2.9% of patients within 90 days of last treatment.1

Closely monitor patients during treatment for signs of infection. Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus.1

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) has been reported after treatment with polatuzumab vedotin-piiq (0.6%, 1/173). Monitor for new or worsening neurological, cognitive, or behavioral changes. Hold polatuzumab vedotin-piiq and any concomitant chemotherapy if PML is suspected, and permanently discontinue if the diagnosis is confirmed.1

Tumor Lysis Syndrome

Polatuzumab vedotin-piiq may cause tumor lysis syndrome. Patients with high tumor burden and rapidly proliferative tumor may be at increased risk of tumor lysis syndrome. Monitor closely and take appropriate measures, including tumor lysis syndrome prophylaxis.1

Hepatotoxicity

Serious cases of hepatotoxicity that were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, have occurred in patients treated with polatuzumab vedotin-piiq.1

In recipients of polatuzumab vedotin-piiq in Study GO29365 (n = 173), Grade 3 and 4 transaminase elevations developed in 1.9% and 1.9%, respectively. Laboratory values suggestive of drug-induced liver injury (both an ALT or AST greater than 3 times upper limit of normal [ULN] and total bilirubin greater than 2 times ULN) occurred in 2.3% of patients.1

Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk of hepatotoxicity. Monitor liver enzymes and bilirubin level.1

Embryo-fetal Toxicity

Based on the mechanism of action and findings from animal studies, polatuzumab vedotin-piiq can cause fetal harm when administered to a pregnant woman. The small molecule component of polatuzumab vedotin-piiq, MMAE, administered to rats caused adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at exposures below those occurring clinically at the recommended dose.1

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with polatuzumab vedotin-piiq and for at least 3 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with polatuzumab vedotin-piiq and for at least 5 months after the last dose.1

Specific Populations

Pregnancy

Risk Summary: Based on findings from animal studies and its mechanism of action, polatuzumab vedotin-piiq 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 polatuzumab vedotin-piiq, MMAE, to pregnant rats during organogenesis at exposures below the clinical exposure at the recommended dose of 1.8 mg/kg polatuzumab vedotin-piiq every 21 days resulted in embryo-fetal mortality and structural abnormalities. Advise a pregnant woman of the potential risks to a fetus.1

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 US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.1

Animal Data: No embryo-fetal development studies in animals have been performed with polatuzumab vedotin-piiq. In an embryo-fetal developmental study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of polatuzumab vedotin-piiq, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities including protruding tongue, malrotated limbs, gastroschisis, and agnathia compared to controls at a dose of 0.2 mg/kg (approximately 0.5-fold the human area under the curve [AUC] at the recommended dose).1

Lactation

Risk Summary: 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 a breastfed child advise women not to breastfeed during treatment with polatuzumab vedotin-piiq and for at least 2 months after the last dose.1

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential prior to initiating polatuzumab vedotin-piiq.1

Polatuzumab vedotin-piiq can cause embryo-fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during treatment with polatuzumab vedotin-piiq and for 3 months after the final dose.1

Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with polatuzumab vedotin-piiq and for at least 5 months after the final dose.1

Based on findings from animal studies, polatuzumab vedotin-piiq may impair male fertility. The reversibility of this effect is unknown.1

Pediatric Use

Safety and effectiveness of polatuzumab vedotin-piiq have not been established in pediatric patients.1

Geriatric Use

Among 173 patients treated with polatuzumab vedotin-piiq 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%). Clinical studies of polatuzumab vedotin-piiq did not include sufficient numbers of patients aged ≥65 to determine whether they respond differently from younger patients. 1

Hepatic Impairment

Avoid the administration of polatuzumab vedotin-piiq in patients with moderate or severe hepatic impairment (bilirubin greater than 1.5 × ULN). Patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions. Polatuzumab vedotin-piiq has not been studied in patients with moderate or severe hepatic impairment. 1

No adjustment in the starting dose is required when administering polatuzumab vedotin-piiq to patients with mild hepatic impairment (bilirubin greater than ULN to less than or equal to 1.5 × ULN or AST greater than ULN).1

Common Adverse Effects

The most common adverse reactions (≥20%) included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Concomitant use of strong CYP3A inhibitors or inducers has the potential to affect the exposure to unconjugated monomethyl auristatin E (MMAE).1

Actions

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.1

Advice to Patients

Peripheral Neuropathy

Advise patients that polatuzumab vedotin-piiq can cause peripheral neuropathy. Advise patients to report to their healthcare provider any numbness or tingling of the hands or feet or any muscle weakness.1

Infusion-Related Reactions

Advise patients to contact their healthcare provider if they experience signs and symptoms of infusion reactions including fever, chills, rash or breathing problems within 24 hours of infusion.1

Myelosuppression

Advise patients to report signs or symptoms of bleeding or infection immediately. Advise patients of the need for periodic monitoring of blood counts.1

Infections

Advise patients to contact their healthcare provider if a fever of 38°C or greater or other evidence of potential infection such as chills, cough, or pain on urination develops. Advise patients of the need for periodic monitoring of blood counts.1

Progressive Multifocal Leukoencephalopathy

Advise patients to seek immediate medical attention for new or changes in neurological symptoms such as confusion, dizziness, or loss of balance; difficulty talking or walking; or changes in vision.1

Tumor Lysis Syndrome

Advise patients to seek immediate medical attention for symptoms of tumor lysis syndrome such as nausea, vomiting, diarrhea, and lethargy.1

Hepatotoxicity

Advise patients to report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.1

Embryo-Fetal Toxicity

Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with polatuzumab vedotin-piiq.1

Females and Males of Reproductive Potential

Advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment with polatuzumab vedotin-piiq and for at least 3 months and 5 months after the last dose, respectively.1

Lactation

Advise women not to breastfeed while receiving polatuzumab vedotin-piiq and for at 2 months after the last dose.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Polatuzumab Vedotin-piiq

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

140 mg

Polivy

Genentech Inc.

AHFS Drug Information. © Copyright 2020, Selected Revisions July 1, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Genentech, Inc. POLIVY (polatuzumab vedotin) INTRAVENOUS prescribing information. 2019 Jun. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=20a16ab2-f338-4abb-9dcd-254bd949a2bc