Polatuzumab vedotin, a CD79b-directed antibody-drug conjugate consisting of a humanized immunoglobulin G1 (IgG1) monoclonal antibody covalently linked to the microtubule inhibitor monomethyl auristatin E (MMAE), is an antineoplastic agent.1, 2, 3, 5, 8
Polatuzumab vedotin-piiq is used in combination with bendamustine and rituximab for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, in patients who have received at least 2 prior therapies.1, 2 The accelerated approval of polatuzumab vedotin for this indication is based on complete response rate; continued approval may be contingent on verification and description of clinical benefit of the drug in a confirmatory study.1 Polatuzumab vedotin has been designated an orphan drug by FDA for the treatment of DLBCL.4
The current indication for polatuzumab vedotin is based principally on the results of an open-label, multicenter phase 2 study (GO29365; NCT02257567) that included a randomized cohort of 80 adults with relapsed or refractory DLBCL after treatment with at least 1 previous regimen.1, 2, 6, 7 Patients included in the study were not candidates for autologous hematopoietic stem cell transplantation (HSCT).1, 2 Patients were randomized to receive therapy with polatuzumab vedotin-piiq (1.8 mg/kg IV on day 2 of cycle 1, then on day 1 of each subsequent 21-day cycle) in combination with bendamustine (90 mg/m2 IV on days 2 and 3 of cycle 1, then on days 1 and 2 of each subsequent 21-day cycle) and rituximab (375 mg/m2 IV on day 1 of each 21-day cycle) or therapy with bendamustine and rituximab alone for up to 6 treatment cycles.1, 2 Patients with grade 2 or higher peripheral neuropathy, active CNS lymphoma, transformed lymphoma, or prior allogeneic HSCT were excluded from the study.1 The median age of patients was 69 years, 66% were male, and 71% were Caucasian; patients received a median of 2 prior therapies and 80% had refractory disease to their last therapy.1, 2 Patients in the polatuzumab vedotin therapy group received a median of 5 cycles of therapy, with 49% receiving 6 cycles; patients in the bendamustine and rituximab alone group received a median of 3 cycles of therapy, with 23% receiving 6 cycles.1
The primary measure of efficacy was complete response (CR) rate at the end of treatment (based on positron emission tomography-computer tomography [PET-CT] imaging using modified Lugano 2014 criteria) as assessed by an independent review committee (IRC); other end points included duration of response and best overall response (CR or partial response [PR]) as assessed by the IRC.1, 2, 7 Patients receiving polatuzumab vedotin in combination with bendamustine and rituximab had a higher CR rate (40 versus 18%) and a higher best overall response rate (63 versus 25%) compared with those receiving bendamustine and rituximab alone.1, 5 Among the 25 patients who achieved a partial or complete response in the polatuzumab vedotin plus bendamustine and rituximab group, 64 and 48% had a duration of response of at least 6 and 12 months, respectively.1 Among the 10 patients who achieved a partial or complete response in the bendamustine and rituximab alone group, 30 and 20% had a duration of response of at least 6 and 12 months, respectively.1 Although progression-free survival and overall survival also appeared to improve with polatuzumab vedotin in combination with bendamustine and rituximab compared with bendamustine and rituximab alone, interpretation of these outcomes is limited due to the small number of events and small sample size.2, 7
To minimize the risk of infusion-related events, the manufacturer recommends a premedication regimen consisting of an antipyretic and an antihistamine at least 30-60 minutes prior to administration of polatuzumab vedotin.1 (See Infusion-related Effects under Cautions: Warnings/Precautions.)
Antiviral and antifungal prophylaxis should be administered as appropriate during therapy.1 (See Infectious Complications under Cautions: Warnings/Precautions.)
Reconstitution and Administration
The usual precautions for handling and preparing solutions of cytotoxic drugs should be observed with polatuzumab vedotin.1
Polatuzumab vedotin-piiq is administered by IV infusion only.1 The initial infusion should be administered over 90 minutes; if the first infusion is well tolerated, subsequent infusions may be administered over 30 minutes.1
Unopened vials of polatuzumab vedotin-piiq powder for injection should be stored at 2-8°C and retained in their original package for protection from light; vials should not be frozen or shaken.1
Prior to administration, commercially available polatuzumab vedotin-piiq lyophilized powder for injection must be reconstituted and diluted.1 The appropriate number of vials should be reconstituted based on the indicated dosage.1 The powder for injection is reconstituted by adding 7.2 mL of sterile water for injection to a vial labeled as containing 140 mg of the drug to provide a solution containing 20 mg/mL.1 The diluent should be directed toward the side of the vial when reconstituting the drug.1 The vial should be gently swirled until the powder is completely dissolved and should not be shaken.1 Following reconstitution, the resulting polatuzumab vedotin solution should be inspected visually for particulate matter and discoloration; the solution should be clear to slightly opalescent, colorless to slightly brown, and free of visible particulates.1 If immediate dilution of the reconstituted solution is not possible, the solution may be stored in the refrigerator (2-8°C) for up to 48 hours or at room temperature (9-25°C) for up to 8 hours.1 The reconstituted solution should not be frozen or exposed to direct sunlight.1
For preparation of the final diluted polatuzumab vedotin-piiq solution for infusion, the required amount of reconstituted drug should be withdrawn from the vial and diluted in an 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.1 Any unused solution left in the vial should be discarded.1 Following dilution, the solution should be gently mixed by slowly inverting the infusion bag; the bag should not be shaken.1 If immediate administration of the diluted solution is not possible, the solution should be stored according to the manufacturer's recommendations based on the diluent used (see Table 1).1 Recommended storage durations include drug transport times; duration of transport should be limited to 30 minutes at 9-25ºC or 12 hours at 2-8°C.1 Because physical agitation of the drug can cause aggregation, care should be taken to limit agitation during preparation and transportation of the drug to the administration site.1
Diluent Used | Storage Durations After Dilution (Including Drug Transport Times) |
|---|---|
0.9% Sodium chloride injection | Up to 4 hours at room temperature (9-25°C) or up to 24 hours under refrigeration (2-8°C); do not freeze or expose to direct sunlight1 |
0.45% Sodium chloride injection | Up to 4 hours at room temperature (9-25°C) or up to 18 hours under refrigeration (2-8°C); do not freeze or expose to direct sunlight1 |
5% Dextrose injection | Up to 6 hours at room temperature (9-25°C) or up to 36 hours under refrigeration (2-8°C); do not freeze or expose to direct sunlight1 |
The manufacturer states that no incompatibilities have been observed between polatuzumab vedotin-piiq solutions and IV infusion bags containing polyvinyl chloride (PVC) or polyolefin (e.g., polyethylene, polypropylene) and with administration sets or aids containing PVC, polyethylene, polyurethane, polybutadiene, acrylonitrile butadiene styrene (ABS), polycarbonate, polyetherurethane, fluorinated ethylene propylene, or polytetrafluoroethylene; in addition, no incompatibilities have been observed with filter membranes composed of polyether sulfone or polysulfone.1
Polatuzumab vedotin-piiq must be administered using a dedicated infusion line equipped with a sterile, nonpyrogenic, low-protein-binding 0.2- or 0.22-µm inline or add-on filter.1 The drug should not be mixed or administered with other drugs.1
For the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior therapies, the recommended adult dosage of polatuzumab vedotin-piiq is 1.8 mg/kg by IV infusion on day 1 of each 21-day cycle 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) for a total of 6 cycles.1
If a dose of polatuzumab vedotin-piiq is missed, the dose should be administered as soon as possible; the schedule of administration should be adjusted to maintain a 21-day interval between doses.1
Dosage Modification for Toxicity
Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of polatuzumab vedotin may be necessary if peripheral neuropathy, infusion-related reactions, or hematologic toxicity occurs.1
If grade 2 or 3 peripheral neuropathy occurs, polatuzumab vedotin therapy should be withheld.1 If the toxicity resolves to grade 1 or less by day 14, therapy may be resumed with the next cycle at a permanently reduced dose of 1.4 mg/kg; if the dose had previously been reduced to 1.4 mg/kg, the drug should be discontinued.1 If grade 2 or 3 peripheral neuropathy persists for more than 14 days following interruption of therapy, polatuzumab vedotin therapy should be discontinued.1 (See Peripheral Neuropathy under Cautions: Warnings/Precautions.)
If grade 4 peripheral neuropathy occurs, polatuzumab vedotin therapy should be discontinued.1
If grade 1 or 2 infusion-related reactions occur, polatuzumab vedotin infusion should be interrupted and supportive treatment provided.1 Upon complete resolution of symptoms, the infusion may be resumed at 50% of the previous infusion rate.1 If no infusion-related reaction occurs, the infusion rate may be increased as tolerated by 50 mg/hour every 30 minutes.1 For the next treatment cycle, the IV infusion should be administered over 90 minutes; if no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes.1 If grade 2 wheezing or urticaria recurs, polatuzumab vedotin therapy should be permanently discontinued.1 (See Infusion-related Effects under Cautions: Warnings/Precautions.)
If grade 3 wheezing, bronchospasm, or generalized urticaria occurs, polatuzumab vedotin therapy should be permanently discontinued.1 If other grade 3 infusion-related reactions occur, the infusion should be interrupted and supportive treatment provided; upon complete resolution of symptoms, the infusion may be resumed at 50% of the previous infusion rate.1 If no infusion-related reaction occurs, the infusion rate may be increased as tolerated by 50 mg/hour every 30 minutes.1 For the next treatment cycle, the IV infusion should be administered over 90 minutes; if no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes.1 If any grade 3 infusion-related reactions recur, polatuzumab vedotin should be permanently discontinued.1
If grade 4 infusion-related reactions occur, the infusion should be stopped immediately and supportive treatment provided; polatuzumab vedotin therapy should be permanently discontinued.1
Treatment delays and dosage reductions may be required if neutropenia or thrombocytopenia occurs during polatuzumab vedotin therapy, unless the primary cause of the hematologic toxicity is lymphoma.1
If grade 3 or 4 neutropenia (absolute neutrophil count [ANC] decreases to less than 1000/mm3 on day 1 of any cycle) occurs, all treatment should be withheld.1 If neutropenia resolves (i.e., ANC exceeds 1000/mm3) by day 7 of the cycle, therapy may be resumed without dosage adjustments; use of a granulocyte colony-stimulating factor (G-CSF) during subsequent cycles should be considered, if not previously given.1 If neutropenia resolves after day 7, all treatment should be restarted and use of a G-CSF during subsequent cycles should be considered, if not previously given.1 If G-CSF prophylaxis was given, a reduced dose of bendamustine should be considered.1 If the dose of bendamustine had previously been reduced, dose reduction of polatuzumab vedotin to 1.4 mg/kg should be considered.1 (See Hematologic Effects under Cautions: Warnings/Precautions.)
If grade 3 or 4 thrombocytopenia (platelet count decreases to less than 75,000/mm3 on day 1 of any cycle) occurs, all treatment should be withheld.1 If thrombocytopenia resolves (i.e., platelet count exceeds 75,000/mm3) by day 7 of the cycle, therapy may be resumed without dosage adjustments.1 If thrombocytopenia resolves after day 7, all treatment should be restarted with a reduced dosage of bendamustine.1 If the dose of bendamustine had previously been reduced, dose reduction of polatuzumab vedotin to 1.4 mg/kg should be considered.1
The manufacturer states that initial dosage adjustment of polatuzumab vedotin-piiq is not necessary in patients with mild hepatic impairment (bilirubin concentrations exceeding, but no more than 1.5 times, the upper limit of normal [ULN] or serum aminotransferase [ALT or AST] concentrations exceeding, but no more than 2.5 times, the ULN).1 Use of polatuzumab vedotin should be avoided in patients with moderate or severe hepatic impairment (bilirubin concentrations exceeding 1.5 times the ULN).1 (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1 (See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
The manufacturer makes no specific dosage recommendations for geriatric patients.1 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
The manufacturer states there are no known contraindications to the use of polatuzumab vedotin.1
Peripheral neuropathy (mainly sensory, but also motor and sensorimotor) has been reported in patients receiving polatuzumab vedotin.1, 2 Peripheral neuropathy may occur as early as the first cycle of therapy and appears to be a cumulative effect.1 In the expanded safety population of 173 patients who received polatuzumab vedotin-piiq in the GO29365 study, new or worsening peripheral neuropathy was reported in 40% of patients; in most cases, peripheral neuropathy was grade 1 (26%), but grade 2 (12%) and grade 3 (2.3%) symptoms also were reported.1, 2 The median time to onset of peripheral neuropathy was 2.1 months.1 Temporary interruption of therapy, dosage reduction, or drug discontinuance was required in some patients.1 Peripheral neuropathy improved or resolved in 65% of patients after a median of 1 month and complete resolution was reported in 48% of the patients.1
Patients receiving polatuzumab vedotin should be monitored for manifestations of peripheral neuropathy (e.g., hypoesthesia, hyperesthesia, paresthesia, dysesthesia, neuropathic pain, burning sensation, weakness, gait disturbance).1 Temporary interruption of therapy, dosage reduction, or drug discontinuance may be required if peripheral neuropathy occurs.1 (See Peripheral Neuropathy under Dosage: Dosage Modification for Toxicity, in Dosage and Administration.)
Infusion-related reactions (e.g., fever, chills, flushing, dyspnea, hypotension, urticaria) have been reported in patients receiving polatuzumab vedotin.1 Such reactions have occurred as late as 24 hours following completion of the infusion.1 In the expanded safety population of 173 patients who received polatuzumab vedotin-piiq in the GO29365 study, infusion-related reactions were reported in 7% of patients; in most cases, the infusion-related reaction was grade 1 (67%), but grade 2 (25%) and grade 3 (8%) symptoms also were reported.1 These infusion-related reactions occurred despite premedication with an antihistamine and an antipyretic in all patients.1
Patients should be monitored closely for infusion reactions during administration of polatuzumab vedotin; monitoring should continue for at least 90 minutes following completion of the initial infusion and for at least 30 minutes following each subsequent infusion.1 To minimize the risk of infusion-related reactions, patients should receive premedication with an antihistamine and antipyretic prior to administration of the drug.1 (See Dosage and Administration: General.) If an infusion-related reaction occurs, the infusion should be interrupted and appropriate treatment provided; a reduction in the infusion rate or temporary or permanent discontinuance of polatuzumab vedotin may be required.1 In patients experiencing a life-threatening reaction, the infusion should be stopped immediately and polatuzumab vedotin therapy should be permanently discontinued.1 (See Infusion-related Reactions under Dosage: Dosage Modification for Toxicity, in Dosage and Administration.)
Severe cytopenias, including neutropenia, thrombocytopenia, and anemia, have been reported in patients receiving polatuzumab vedotin.1, 2 Severe (grade 3 or higher) thrombocytopenia, anemia, lymphopenia, neutropenia, or febrile neutropenia occurred in 40, 24, 13, 42, or 11%, respectively, of patients receiving polatuzumab vedotin-piiq in combination with bendamustine and rituximab in the GO29365 study; grade 4 thrombocytopenia, lymphopenia, neutropenia, or febrile neutropenia occurred in 16, 9, 24, or 4.4%, respectively, of these patients.1 A higher incidence of severe cytopenias was observed in patients receiving the combination regimen of polatuzumab vedotin, bendamustine, and rituximab compared with bendamustine and rituximab alone in this study, but this was not associated with an increased rate of infections or need for transfusion.2 Cytopenias resulted in the discontinuance of polatuzumab therapy in 18% of patients and was the most common reason for treatment discontinuance.1 A granulocyte colony-stimulating factor (G-CSF) was administered in 42% of patients in the study.1
Complete blood cell (CBC) counts should be monitored during therapy.1 If cytopenias occur, temporary interruption of therapy, dosage reduction, or drug discontinuance may be required.1 Prophylactic use of a G-CSF should be considered.1 (See Hematologic Toxicity under Dosage: Dosage Modification for Toxicity, in Dosage and Administration.)
Serious and sometimes fatal opportunistic infections, such as sepsis, pneumonia (e.g., Pneumocystis jiroveci ), herpes virus infection, and cytomegalovirus infection, have been reported in patients receiving polatuzumab vedotin.1 In the expanded safety population of 173 patients who received polatuzumab vedotin-piiq in the GO29365 study, grade 3 or 4 infections occurred in 32% of patients; infection-related fatalities were reported in 2.9% of patients within 90 days of the last dose.1
Patients should be closely monitored for signs and symptoms of infection.1 Antifungal and antiviral prophylaxis for Pneumocystis jiroveci and herpes virus infections is recommended during polatuzumab vedotin therapy.1
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) has been reported in patients receiving polatuzumab vedotin.1 Patients should be monitored for any new or worsening neurologic, cognitive, or behavioral changes suggestive of PML (e.g., confusion, dizziness, loss of balance, vision changes, changes in speech or walking).1 If PML is suspected, polatuzumab vedotin and any concomitant chemotherapy should be withheld; if PML is confirmed, polatuzumab vedotin therapy should be permanently discontinued.1
Tumor lysis syndrome has been reported in patients receiving polatuzumab vedotin.1 The risk is increased in patients with large tumor burden and rapidly proliferating tumors.1 Such patients should be closely monitored for manifestations of tumor lysis syndrome (e.g., nausea, vomiting, diarrhea, lethargy) and appropriate measures, including prophylactic therapy, should be employed.1
Hepatotoxicity (i.e., findings suggestive of hepatocellular injury, including elevations in serum aminotransferases [ALT or AST] and bilirubin concentrations) has been reported in patients receiving polatuzumab vedotin therapy.1 In the expanded safety population of 173 patients who received polatuzumab vedotin-piiq in the GO29365 study, severe elevations in aminotransferase concentrations (grade 3 and 4) occurred in 1.9% of patients receiving the drug.1 Increases in ALT or AST concentrations to greater than 3 times the upper limit of normal (ULN) and total bilirubin concentrations greater than 2 times the ULN were reported in 2.3% of patients receiving the drug.1
The risk of hepatotoxicity may be increased in patients with preexisting liver disease or elevated liver enzymes at baseline and those receiving other potentially hepatotoxic drugs.1 Liver function tests should be monitored during polatuzumab vedotin therapy.1
Fetal/Neonatal Morbidity and Mortality
There are no available data regarding the risk of polatuzumab vedotin use in pregnant women; however, based on its mechanism of action and animal findings, the drug may cause fetal harm.1 Embryofetal toxicity (e.g., structural abnormalities, embryofetal death) has been observed following administration of the cytotoxic component of polatuzumab vedotin (monomethyl auristatin E [MMAE]) to pregnant rats at exposure levels approximately 0.5 times the human exposure at the recommended dosage.1
Pregnancy should be avoided during polatuzumab vedotin therapy.1 The manufacturer recommends confirmation of pregnancy status prior to initiation of polatuzumab vedotin, and women of childbearing potential should be advised to use effective contraceptive methods during and for at least 3 months after the last dose.1 In addition, men with female partners of childbearing potential should use effective methods of contraception during and for at least 5 months after the last dose.1 Patients should be apprised of the potential hazard to the fetus if polatuzumab vedotin is used during pregnancy.1
As with all therapeutic proteins, there is a potential for immunogenicity with polatuzumab vedotin.1 Across all clinical studies, anti-polatuzumab vedotin-piiq antibodies were detected in 2.6% of evaluable patients receiving the drug.1 In the GO29365 study, antibodies to polatuzumab vedotin-piiq were detected in 6% of patients across all study arms.1 The clinical relevance of such antibodies is not known.1
Results of animal studies suggest that polatuzumab vedotin may impair male fertility.1
Polatuzumab vedotin may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)
It is not known whether polatuzumab vedotin is distributed into milk in humans.1 Because of the potential for serious adverse reactions to polatuzumab vedotin in nursing infants, women should be advised to discontinue nursing while receiving the drug and for at least 2 months after the last dose.1 The effects of the drug on nursing infants or on milk production are unknown.1
Safety and efficacy of polatuzumab vedotin have not been established in pediatric patients.1
Among patients treated with polatuzumab vedotin-piiq in the GO29365 study, 55% were 65 years of age or older.1 Serious adverse effects occurred more frequently in these geriatric patients compared with younger adults.1 Clinical studies of polatuzumab vedotin did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger patients.1
Clinically important differences in the pharmacokinetics of polatuzumab vedotin based on age have not been observed.1
Exposure to monomethyl auristatin E (MMAE), the cytotoxic component of polatuzumab vedotin, may be increased in patients with hepatic impairment.1 Following administration of polatuzumab vedotin, systemic exposure of MMAE was increased by 40% in patients with mild hepatic impairment (bilirubin concentrations exceeding, but no more than 1.5 times, the ULN or ALT/AST concentrations exceeding, but no more than 2.5 times, the ULN); however, the increase was not considered clinically important and no dosage adjustment is necessary in such patients.1
Safety and pharmacokinetics of polatuzumab vedotin in patients with moderate or severe hepatic impairment (bilirubin concentrations exceeding 1.5 times the ULN or ALT/AST concentrations exceeding 2.5 times the ULN) or in liver transplant patients are not known.1, 7 However, systemic exposure of MMAE is expected to be increased in such patients, which may increase the risk of adverse reactions.1 Use of polatuzumab vedotin is not recommended in patients with moderate or severe hepatic impairment.1
Analysis of available pharmacokinetic data indicate that mild or moderate renal impairment (creatinine clearance of 30-89 mL/minute) does not substantially affect the pharmacokinetics of polatuzumab vedotin (both the antibody-drug conjugate and the MMAE component).1
Polatuzumab vedotin has not been studied in patients with severe renal impairment (creatinine clearance of 15-29 mL/minute) or end-stage renal disease (including those requiring dialysis).1
Adverse effects reported in 20% or more of patients with diffuse large B-cell lymphoma (DLBCL) receiving polatuzumab vedotin-piiq in combination with bendamustine and rituximab include neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia.1
Clinical drug interaction studies have not been performed with polatuzumab vedotin; information to date is based on in vitro studies and pharmacokinetic modeling.1 In vitro studies indicate that monomethyl auristatin E (MMAE), the cytotoxic component of polatuzumab vedotin, is a substrate of cytochrome P-450 (CYP) isoenzyme 3A4.1 (See Description.) In vitro studies also indicate that MMAE does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 2D6 and does not induce major CYP isoenzymes.1 MMAE is a substrate of P-glycoprotein (P-gp), but does not inhibit P-gp.1
Drugs Affecting Hepatic Microsomal Enzymes
Concomitant use of polatuzumab vedotin with potent inhibitors of CYP3A may increase systemic exposure of MMAE, thereby increasing the risk of drug toxicity.1 Patients receiving such concomitant therapy should be monitored for signs of toxicity.1 Pharmacokinetic modeling studies predict that concomitant use of polatuzumab vedotin with the potent CYP3A inhibitor ketoconazole is expected to increase the area under the plasma concentration-time curve (AUC) of unconjugated MMAE by 45%.1
Concomitant use of polatuzumab vedotin with potent inducers of CYP3A may decrease systemic exposure of MMAE.1 Pharmacokinetic modeling studies predict that concomitant use of polatuzumab vedotin with the potent CYP3A inducer rifampin is expected to decrease the AUC of unconjugated MMAE by 63%.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP3A Isoenzymes
Based on pharmacokinetic modeling, polatuzumab vedotin is not expected to alter the systemic exposure of midazolam, a sensitive CYP3A substrate.1
Clinically important changes in the pharmacokinetics of polatuzumab vedotin or MMAE were not observed in a population pharmacokinetic analysis.1
Clinically important changes in the pharmacokinetics of polatuzumab vedotin or MMAE were not observed in a population pharmacokinetic analysis.1
Polatuzumab vedotin, a CD79b-directed antibody-drug conjugate, is an antineoplastic agent.1, 2, 3, 5, 8 The antibody-drug conjugate consists of a recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for human CD79b covalently attached to a cytotoxic component, the microtubule inhibitor monomethyl auristatin E (MMAE), via a protease-cleavable linker.1, 2, 3 MMAE is a synthetic analog of dolastatin, a naturally occurring product isolated from the sea hare Dolabella auriculara .1, 3 A dipeptide bond covalently links MMAE to the antibody component;1, 2, 3 on average, 3.5 molecules of MMAE are attached to each antibody molecule.1 The antibody portion of polatuzumab vedotin binds specifically to CD79b, a B-cell receptor component expressed on the surface of mature B cells and most malignant B cells, including more than 95% of diffuse large B-cell lymphoma (DLBCL).1, 2, 3, 5, 7 Following binding of the antibody portion of polatuzumab vedotin to CD79b, the resultant complex is internalized by the cell.1 The cytotoxic component MMAE is then released via proteolytic cleavage of the dipeptide bond and binds to tubulin, resulting in inhibition of cell division and apoptosis.1
Systemic exposure of polatuzumab vedotin (both the antibody-drug conjugate and unconjugated MMAE) increases in a dose proportional manner over the dose range of 1.2-2.4 mg/kg.1 The antibody-drug conjugate is expected to be degraded into small peptides, amino acids, unconjugated MMAE and catabolites of unconjugated MMAE.1 MMAE is metabolized in the liver, principally by cytochrome P-450 (CYP) 3A4, and is 71-77% bound to plasma proteins.1 The terminal half-lives of the antibody-drug conjugate and MMAE are approximately 12 and 4 days, respectively.1 Population pharmacokinetic analyses indicate that age (range of 20-89 years), gender, and race (Asian versus non-Asian) do not appear to have clinically important effects on the pharmacokinetics of the antibody-drug conjugate.1
Risk of peripheral neuropathy.1 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).1
Risk of infusion-related reactions.1 Importance of reporting any signs and symptoms of such reactions (e.g., fever, chills, rash, breathing difficulty) that occur within 24 hours of an infusion of the drug.1
Risk of hematologic toxicity.1 Importance of immediately informing clinician if signs or symptoms of myelosuppression (e.g., infection, bleeding/hemorrhage) develop.1 Importance of the need to periodically monitor blood cell counts.1
Risk of infections.1 Importance of informing clinician if signs or symptoms suggestive of an infection (e.g., fever, chills, cough, painful urination) develop.1
Risk of progressive multifocal leukoencephalopathy (PML).1 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.1
Risk of tumor lysis syndrome.1 Importance of seeking immediate medical attention if symptoms (e.g., nausea, vomiting, diarrhea, lethargy) occur.1
Risk of hepatotoxicity.1 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.1
Risk of fetal harm.1 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 at least 3 and 5 months, respectively, after discontinuance of therapy.1 Importance of women informing clinicians if they are or plan to become pregnant.1 If pregnancy occurs, advise the patient of the potential risk to the fetus.1
Importance of advising women to avoid breast-feeding during polatuzumab vedotin therapy and for at least 2 months after discontinuance of the drug.1
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.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion only | 140 mg | Genentech |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions August 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Genentech Inc. Polivy® (polatuzumab vedotin-piiq) injection for IV infusion prescribing information. South San Francisco, CA; 2019 Jun.
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3. Yu B, Liu D. Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma. J Hematol Oncol. 2019;12(1):94 [PubMed 31500657]
4. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2019 Oct 9. [Web]
5. Deeks, ED. Polatuzumab Vedotin: First Global Approval. Drugs . 2019; 79:1467-75. [PubMed 31352604]
6. Sehn LH,, Matasar MJ,, Flowers CR, et al. Polatuzumab Vedotin Plus Bendamustine with Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Updated Results of a Phase Ib/II Randomized Study. Blood . 2019; 134:4081. [Web]
7. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761121Orig1s000: Summary Review. From FDA website. [Web]
8. Skrabek P, Assouline S, Christofides A et al. Emerging therapies for the treatment of relapsed or refractory diffuse large B cell lymphoma. Curr Oncol . 2019; 26:253-65. [PubMed 31548805]