Class: Antineoplastic Agents
Chemical Name: Anti-(human antigen CD79b) (human-Mus musculus monoclonal MCDS4409A heavy chain), disulfide with human-Mus musculus monoclonal MCDS4409A k-chain thioether with maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl monomethylauristatin E immunoglobulin G1 dimer
Molecular Formula: C6670H10371N1745O2087S40
CAS Number: 1313206-42-6
Antineoplastic agent; an anti-CD79b antibody conjugated with a microtubule inhibitor (monomethyl auristatin E [MMAE]).
Uses for Polatuzumab Vedotin-piiq
Used in combination with bendamustine and rituximab for treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, in patients who have received at least 2 prior therapies; designated an orphan drug by FDA for treatment of this cancer.
Accelerated approval based on complete response rate; continued approval may be contingent on verification and description of clinical benefit in a confirmatory study.
Polatuzumab Vedotin-piiq Dosage and Administration
To minimize risk of infusion-related events, premedication with an antipyretic and antihistamine is recommended at least 30–60 minutes prior to administration. (See Infusion-related Effects under Cautions.)
Initiate antiviral and antifungal prophylaxis as appropriate. (See Infectious Complications under Cautions.)
Consult specialized references for procedures for proper handling and disposal of antineoplastics.
For solution compatibility information, see Compatibility under Stability.
Administer by IV infusion only.
Must reconstitute and dilute the commercially available powder for injection prior to administration.
Do not mix or administer with any other drug.
No incompatibilities observed with IV infusion bags containing polyvinyl chloride (PVC) or polyolefin (e.g., polyethylene, polypropylene) and with administration sets containing PVC, polyethylene, polyurethane, polybutadiene, acrylonitrile butadiene styrene (ABS), polycarbonate, polyetherurethane, fluorinated ethylene propylene, or polytetrafluoroethylene; in addition, no incompatibilities observed with filter membranes composed of polyether sulfone or polysulfone.
Administer through a dedicated line with a sterile, nonpyrogenic, low-protein-binding 0.2- or 0.22-µm inline or add-on filter.
Physical agitation of the drug can cause aggregation; limit agitation during preparation and transportation.
Reconstitute vial labeled as containing 140 mg of polatuzumab vedotin-piiq with 7.2 mL of sterile water for injection to provide a solution containing 20 mg/mL; direct diluent toward side of the vial. Gently swirl vial until powder is completely dissolved. Do not shake.
Reconstituted solution should be clear to slightly opalescent, colorless to slightly brown, and free of visible particulates.
If immediate dilution of the reconstituted solution is not possible, store solution according to manufacturer's guidelines. (See Storage under Stability.)
Dilute appropriate dose in an IV infusion bag containing a minimum volume of 50 mL of 0.9% sodium chloride injection, 0.45% sodium chloride injection, or 5% dextrose injection to a final concentration of 0.72–2.7 mg/mL. Gently mix diluted solution by slowly inverting infusion bag; do not shake. Discard any unused portions of vial.
If immediate administration of the diluted solution is not possible, store solution according to manufacturer's guidelines. (See Storage under Stability.)
Rate of Administration
Administer initial IV infusion over 90 minutes; if first infusion is well tolerated, may administer subsequent infusions over 30 minutes.
1.8 mg/kg by IV infusion on day 1 of each 21-day cycle for a total of 6 cycles; administer in combination with bendamustine (90 mg/m2 IV on days 1 and 2 of each cycle) and rituximab (375 mg/m2 IV on day 1 of each cycle).
If a dose is missed, administer the dose as soon as possible; adjust schedule of administration to maintain a 21-day interval between polatuzumab vedotin doses.
Dosage Modification for Toxicity
May need to interrupt therapy, reduce dosage, and/or permanently discontinue therapy if peripheral neuropathy, infusion-related reactions, or hematologic toxicity occurs.
If grade 2 or 3 peripheral neuropathy occurs, interrupt therapy. When toxicity resolves to grade ≤1 by day 14, may resume therapy with next cycle at a permanently reduced dose of 1.4 mg/kg; if a dose reduction to 1.4 mg/kg had previously occurred, discontinue drug. If grade 2 or 3 peripheral neuropathy persists for >14 days following interruption of therapy, discontinue therapy. (See Peripheral Neuropathy under Cautions.)
If grade 4 peripheral neuropathy occurs, discontinue polatuzumab vedotin.
If grade 1 or 2 infusion-related reactions occur, interrupt infusion and provide supportive treatment. When symptoms completely resolve, may resume infusion at 50% of the previous infusion rate. If no infusion-related reaction occurs, may increase infusion rate as tolerated by 50 mg/hour every 30 minutes. For the next treatment cycle, administer IV infusion over 90 minutes; if no infusion-related reaction occurs, may administer subsequent infusions over 30 minutes. If grade 2 wheezing or urticaria recurs, permanently discontinue polatuzumab vedotin. (See Infusion-related Effects under Cautions.)
If grade 3 wheezing, bronchospasm, or generalized urticaria occurs, permanently discontinue therapy. If other grade 3 infusion-related reactions occur, interrupt infusion and provide supportive treatment. When symptoms completely resolve, may resume infusion at 50% of the previous infusion rate. If no infusion-related reaction occurs, may increase infusion rate as tolerated by 50 mg/hour every 30 minutes. For the next treatment cycle, administer IV infusion over 90 minutes; if no infusion-related reaction occurs, may administer subsequent infusions over 30 minutes. If any grade 3 infusion-related symptoms recur, permanently discontinue therapy.
If grade 4 infusion-related reactions occur, immediately stop infusion and provide supportive treatment; permanently discontinue polatuzumab vedotin therapy.
Treatment delays and dosage reductions may be required if neutropenia or thrombocytopenia occurs unless primary cause is lymphoma. (See Hematologic Effects under Cautions.)
If grade 3 or 4 neutropenia (ANC <1000/mm3 on day 1 of any cycle) occurs, withhold all treatment. If neutropenia resolves (i.e., ANC >1000/mm3) by day 7, may resume therapy without dosage adjustments; consider use of a granulocyte colony-stimulating factor (G-CSF) for subsequent cycles, if not previously given. If neutropenia resolves after day 7, restart all treatment; consider use of G-CSF for subsequent cycles if not previously given. If G-CSF prophylaxis was given, consider a dose reduction of bendamustine. If dose of bendamustine had previously been reduced, consider dose reduction of polatuzumab vedotin to 1.4 mg/kg.
If grade 3 or 4 thrombocytopenia (platelet count <75,000/mm3 on day 1 of any cycle) occurs, withhold all treatment. If thrombocytopenia resolves (i.e., platelet count >75,000/mm3) by day 7, may resume all treatment without dosage adjustments. If thrombocytopenia resolves after day 7, restart all treatment with a reduced dose of bendamustine. If dose of bendamustine had previously been reduced, consider dose reduction of polatuzumab vedotin to 1.4 mg/kg.
Mild hepatic impairment (bilirubin concentrations >1 to 1.5 times the ULN or ALT/AST >1 to 2.5 times the ULN): No initial dosage adjustment required. (See Special Populations under Pharmacokinetics: Absorption.)
Moderate or severe hepatic impairment (bilirubin concentrations >1.5 times the ULN or ALT/AST >2.5 times the ULN): Use not recommended. (See Hepatic Impairment under Cautions.)
No specific dosage recommendations. (See Renal Impairment under Cautions.)
No specific dosage recommendations. (See Geriatric Use under Cautions.)
Cautions for Polatuzumab Vedotin-piiq
No known contraindications.
Risk of peripheral neuropathy (mainly sensory, but also motor and sensorimotor); may occur as early as the first cycle of therapy and appears to be a cumulative effect. Median time to onset is 2 months.
Monitor patients for manifestations of peripheral neuropathy (e.g., hypoesthesia, hyperesthesia, paresthesia, burning sensation, neuropathic pain, weakness, gait disturbance). If such symptoms occur, temporary interruption of therapy, dosage reduction, or drug discontinuance may be required. (See Dosage Modification for Toxicity under Dosage and Administration.)
Infusion-related reactions (e.g., fever, chills, flushing, dyspnea, hypotension, urticaria), sometimes severe, reported; may occur as late as 24 hours following infusion.
Premedicate with an antihistamine and antipyretic prior to administration. Monitor patient during and for at least 90 minutes following completion of initial infusion and for at least 30 minutes following completion of each subsequent infusion.
If an infusion-related reaction occurs, interrupt infusion and provide appropriate treatment; reduction in infusion rate or temporary or permanent discontinuance of therapy may be required. (See Dosage Modification for Toxicity under Dosage and Administration.)
Risk of severe cytopenias (e.g., neutropenia, thrombocytopenia, anemia).
Monitor CBCs closely during therapy. If cytopenias occur, temporary interruption of therapy, dosage reduction, or drug discontinuance may be required. Consider G-CSF prophylaxis. (See Dosage Modification for Toxicity under Dosage and Administration.)
Serious and sometimes fatal opportunistic infections (i.e., sepsis, pneumonia [including Pneumocystis jiroveci], herpes virus infection, cytomegalovirus infection) reported.
Monitor for signs and symptoms of infection. Antifungal and antiviral prophylaxis for Pneumocystis jiroveci and herpes virus infections recommended.
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) reported.
Monitor patients for new or worsening neurological, cognitive, or behavioral changes suggestive of PML. (See Advice to Patients.) If PML is suspected, withhold polatuzumab vedotin and any concomitant chemotherapy. If PML is confirmed, permanently discontinue therapy.
Tumor Lysis Syndrome
Tumor lysis syndrome reported. Increased risk in patients with large tumor burden and rapidly proliferating tumors; closely monitor such patients and take appropriate precautions, including administration of prophylaxis. (See Advice to Patients.)
Hepatotoxicity (e.g., elevations in ALT, AST, and/or bilirubin concentrations consistent with hepatocellular injury) reported. Increased risk in patients with preexisting liver disease or elevated liver enzymes at baseline and those receiving other potentially hepatotoxic drugs.
Monitor serum ALT, AST, and total bilirubin concentrations during therapy.
Fetal/Neonatal Morbidity and Mortality.
May cause fetal harm. Embryofetal toxicity observed in animals exposed to the cytotoxic component of the drug (MMAE).
Verify pregnancy status prior to initiating therapy. Avoid pregnancy during therapy. Women of childbearing potential and men who are partners of such women should use effective contraception while receiving polatuzumab vedotin and for ≥3 months and ≥5 months, respectively, after the drug is discontinued.
If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.
Antibodies to polatuzumab vedotin reported. Clinical relevance not known.
Impairment of Fertility
Results of animal studies suggest that polatuzumab vedotin may impair male fertility.
May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Not known whether polatuzumab vedotin is distributed into human milk. Effects on nursing infants and milk production also unknown. Discontinue nursing during therapy and for ≥2 months after discontinuance of the drug.
Safety and efficacy not established.
In the principal clinical trial, 55% of patients who received polatuzumab vedotin were ≥65 years of age. Serious adverse effects occurred more frequently in such patients compared with younger patients.
Insufficient experience in patients ≥65 years of age to determine whether they respond differently from younger adults.
Systemic exposure of MMAE (cytotoxic component of the antibody-drug conjugate) may be increased in patients with hepatic impairment. (See Special Populations under Pharmacokinetics: Absorption.)
Patients with moderate or severe hepatic impairment (bilirubin concentrations >1 to 1.5 times the ULN or ALT/AST >1 to 2.5 times the ULN) may be at increased risk of adverse effects as a result of increased exposure to MMAE; use not recommended.
Pharmacokinetics do not appear to be substantially affected by mild or moderate renal impairment (Clcr 30–80 mL/minute).
Not studied in patients with severe renal impairment (Clcr 15–29 mL/minute) or end-stage renal disease (with or without dialysis).
Common Adverse Effects
Neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, pneumonia.
Interactions for Polatuzumab Vedotin-piiq
MMAE (the cytotoxic component of polatuzumab vedotin) is a substrate of CYP3A4. MMAE does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 2D6 and does not induce major CYP isoenzymes.
MMAE is a substrate of P-glycoprotein (P-gp), but does not inhibit P-gp.
Drugs Affecting Hepatic Microsomal Enzymes
Potent inhibitors of CYP3A: Possible increased systemic exposure of MMAE and increased risk of toxicity. Monitor patients closely for signs of toxicity.
Potent inducers of CYP3A: Possible decreased systemic exposure of MMAE.
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP3A: Pharmacokinetic interaction not expected.
Clinically important changes in polatuzumab vedotin or MMAE pharmacokinetics not observed based on population pharmacokinetic analysis
Increased systemic exposure of MMAE by about 45% expected based on pharmacokinetic modeling
Monitor closely for signs of toxicity
No change in systemic exposure of midazolam expected
Decreased systemic exposure of MMAE by about 63% expected based on pharmacokinetic modeling
Clinically important changes in polatuzumab vedotin or MMAE pharmacokinetics not observed based on population pharmacokinetic analysis
Polatuzumab Vedotin-piiq Pharmacokinetics
AUCs of the antibody-drug conjugate and unconjugated MMAE are dose proportional over the range of 1.2–2.4 mg/kg.
Patients with mild hepatic impairment (bilirubin concentrations >1 to 1.5 times the ULN or ALT/AST >1 to 2.5 the ULN): Systemic exposure of MMAE is increased by 40%; however, not considered clinically important.
Not known whether polatuzumab vedotin is distributed into milk.
Plasma Protein Binding
Antibody-drug conjugate expected to be degraded into small peptides, amino acids, unconjugated MMAE, and catabolites of unconjugated MMAE.
MMAE is metabolized in the liver, principally by CYP3A4.
Antibody-drug conjugate: Approximately 12 days.
MMAE: Approximately 4 days.
Mild or moderate renal impairment (Clcr 30–89 mL/minute): No clinically important changes in pharmacokinetics of antibody-drug conjugate or unconjugated MMAE observed.
Severe renal impairment (Clcr 15–29 mL/minute) or end-stage renal disease (with or without dialysis): Effects on pharmacokinetics of antibody-drug conjugate or unconjugated MMAE not known.
Age, gender, and race: No clinically important pharmacokinetic changes observed.
Powder for Injection
Unopened vials: 2–8°C in original package to protect from light. Do not freeze.
Reconstituted drug: If not used immediately, may store at 2–8°C for ≤48 hours or 9–25°C for ≤8 hours. Do not freeze or expose to direct sunlight.
Diluted infusion solutions in 0.9% sodium chloride: If not used immediately, may store at 2–8°C for ≤24 hours or at room temperature (9–25°C) for ≤4 hours; do not freeze or expose to direct sunlight. Total storage plus drug transport times should not exceed these storage durations; limit transport times to 30 minutes at 9–25°C or 12 hours at 2–8°C.
Diluted infusion solutions in 0.45% sodium chloride: If not used immediately, may store at 2–8°C for ≤18 hours or at room temperature (9–25°C) for ≤4 hours; do not freeze or expose to direct sunlight. Total storage plus drug transport times should not exceed these storage durations; limit transport times to 30 minutes at 9–25°C or 12 hours at 2–8°C.
Diluted infusion solutions in 5% dextrose: If not used immediately, may store at 2–8°C for ≤36 hours or at room temperature (9–25°C) for ≤6 hours; do not freeze or expose to direct sunlight. Total storage plus drug transport times should not exceed these storage durations; limit transport times to 30 minutes at 9–25°C or 12 hours at 2–8°C.
For information on systemic interactions resulting from concomitant use, see Interactions.
Dextrose 5% in water
Sodium chloride 0.45%
Sodium chloride 0.9%
Antibody-drug conjugate consisting of a recombinant humanized IgG1 monoclonal antibody specific for human CD79b covalently attached to the cytotoxic microtubule inhibitor MMAE via a protease-cleavable linker. Average of 3.5 molecules of MMAE are attached to each antibody molecule.
The antibody-drug conjugate binds specifically to CD79b, a B-cell receptor component expressed on the surface of mature B cells and most malignant B cells, including >95% of DLBCL. The resultant complex is internalized by the cell, and MMAE is released via proteolytic cleavage. The cytotoxic MMAE component then binds to tubulin, resulting in inhibition of cell division and apoptosis.
Advice to Patients
Risk of peripheral neuropathy. Importance of informing clinician of new or worsening symptoms of peripheral neuropathy (e.g., tingling or numbness of the hands or feet, any muscle weakness).
Risk of infusion-related reactions. Importance of reporting signs and symptoms of such reactions (e.g., fever, chills, rash, or breathing difficulty) that occur within 24 hours of an infusion of the drug.
Risk of hematologic toxicity. Importance of immediately informing clinician if signs or symptoms of myelosuppression (e.g., infection, bleeding/hemorrhage) develop. Importance of the need to periodically monitor blood cell counts.
Risk of infections. Importance of informing clinician if signs or symptoms suggestive of an infection (e.g., fever, chills, cough, painful urination) develop.
Risk of PML. Importance of seeking immediate medical attention if signs or symptoms suggestive of PML (e.g., confusion, dizziness, loss of balance, changes in speech or walking, changes in vision) occur.
Risk of tumor lysis syndrome. Importance of seeking immediate medical attention if symptoms (e.g., nausea, vomiting, diarrhea, lethargy) occur.
Risk of hepatotoxicity. Importance of advising patients to report possible symptoms of liver injury (e.g., fatigue, anorexia, right upper quadrant abdominal pain, jaundice, dark urine) to their clinician.
Risk of fetal harm. Necessity of advising women of childbearing potential and men who are partners of such women that they should use effective contraception while receiving the drug and for ≥3 months and ≥5 months, respectively, after discontinuance of therapy. Importance of women informing clinicians if they are or plan to become pregnant. If pregnancy occurs, advise the patient of potential risk to the fetus.
Importance of advising women to avoid breast-feeding during therapy and for ≥2 months after discontinuance of the drug.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)
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.
For injection, for IV infusion only
AHFS DI Essentials™. © Copyright 2022, Selected Revisions September 28, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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