Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
polatuzumab vedotin
Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate which consists of a humanized IgG1 monoclonal antibody and an anti-mitotic agent, monomethyl auristatin E (MMAE) covalently attached by a cleavable linker. Upon binding to CD79b on the surface of B cells, polatuzumab vedotin is endocytosed. Once inside the cell, lysosomal proteases cleave the linker enabling intracellular delivery of MMAE. The released MMAE binds to microtubules and kills dividing cells by inhibiting cell division (G2/M phase) and inducing apoptosis.
| Peak plasma levels | Unconjugated MMAE: ~2.5 days (after first dose) |
| PPB | MMAE: 71% - 77% |
Polatuzumab vedotin undergoes catabolism to produce small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE related catabolites.
| Half-life | Antibody-conjugated MMAE: ~ 12 days (at cycle 6) Unconjugated MMAE: ~ 4 days (after first dose) |
| Feces | Majority of MMAE excreted in feces |
- Diffuse large B-cell lymphoma (DLBCL)
(Includes conditional approvals)
Refer to the product monograph for a full list and details of approved indications
Emetogenic Potential:
The following table lists adverse effects that occurred in ≥5% of relapsed or refractory DLBCL patients treated with polatuzumab vedotin in combination with bendamustine and rituximab compared with bendamustine and rituximab alone. It also includes severe, life-threatening and post-marketing adverse effects from other sources.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Hypotension (9%) | E | |||
| Tachycardia (9%) | E | ||||
| Dermatological | Rash, pruritus (13%) | E | |||
| Gastrointestinal | Abdominal pain (11%) | E | |||
| Anorexia, weight loss (27%) | E | ||||
| Constipation (18%) | E | ||||
| Diarrhea (38%) | E | ||||
| Gastroesophageal reflux disease (7%) | E | ||||
| Nausea, vomiting (33%) (2% severe) | E | ||||
| General | Fatigue (40%) | E | |||
| Hematological | Myelosuppression ± infection (47%) (including anemia) (40% severe) | E | |||
| Hepatobiliary | Hepatotoxicity (4%) (severe) | E | |||
| ↑ LFTs (9%) | E | ||||
| ↑ Lipase (7%) | E | ||||
| Hypersensitivity | Infusion related reaction (33%) (may be severe) | I E | |||
| Metabolic / Endocrine | Abnormal electrolyte(s) (16%) (↓ K, ↓ albumin, ↓ Ca, ↓ PO4) | E | |||
| Tumor lysis syndrome (8%) | E | ||||
| Musculoskeletal | Musculoskeletal pain (7%) | E | |||
| Nervous System | Anxiety (7%) | E | |||
| Dizziness (13%) | E | ||||
| Dysgeusia (7%) | E | ||||
| Headache (9%) | E | ||||
| Insomnia (9%) | E | ||||
| Leukoencephalopathy - Progressive multifocal leukoencephalopathy (PML) (rare) | E | ||||
| Peripheral neuropathy (20%) (0% severe) | E | ||||
| Respiratory | Cough, dyspnea (16%) | E | |||
| Pneumonitis (4%) | E | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common side effects for polatuzumab vedotin include myelosuppression ± infection, fatigue, diarrhea, infusion related reactions, nausea, vomiting, anorexia, weight loss, peripheral neuropathy, constipation, abnormal electrolyte(s), and rash/pruritus.
Infusion-related reactions, including severe cases have been reported. Symptoms include fever, chills, flushing, dyspnea, hypotension, and urticaria and may be delayed, occurring as late as 24 hours after administration.
Tumor lysis syndrome (TLS) may occur; risk of TLS is higher in patients with a high tumor burden and/or with rapid tumor proliferation.
Hepatotoxicity may be increased in patients with preexisting liver disease, elevated baseline liver enzymes, and/or concomitant hepatotoxic medication. Most events were low grade and reversible.
Serious, life-threatening, or fatal infections, including opportunistic infections such as pneumonia (including Pneumocystis jirovecii and other fungal pneumonia), bacteremia, sepsis, herpes zoster infection, and cytomegalovirus infection have been reported. Cases of progressive multifocal leukoencephalopathy (PML) have been observed.
Peripheral neuropathy has been reported and can occur as early as the first cycle of treatment with increasing risk after sequential doses, but no grade 3-5 events were reported. Patients with pre-existing peripheral neuropathy may experience worsening of their condition. Peripheral neuropathy is primarily sensory; however, motor and sensorimotor peripheral neuropathy may also occur. The median time to onset was 1.8 months. Neuropathy completely resolved in 61% of patients.
Refer to protocol by which patient is being treated.
Premedication (Prophylaxis for Infusion Reactions):
- If not already pre-medicated, administer an antihistamine and anti-pyretic at least 30 to 60 minutes prior to polatuzumab vedotin administration.
Other Supportive Care:
- Administer tumor lysis syndrome prophylaxis for patients at increased risk of tumor lysis syndrome.
- Consider anti-infective prophylaxis. (e.g., PJP, herpes virus)
- Consider prophylactic G-CSF administration for neutropenia.
- Administer in combination with bendamustine and rituximab (for relapsed/refractory DLBCL). Refer to BEND+POLA+RITU for bendamustine and rituximab dosing.
Dose levels - Relapsed/Refractory DLBCL:
| Dose level | Polatuzumab vedotin Dose (mg/kg)* |
| 0 | 1.8 |
| -1 | 1.4 |
| -2 | Discontinue |
*Do not re-escalate once dose is decreased
Dose Modifications - Relapsed/Refractory DLBCL:
Toxicity on Day 1 of any cycle | Grade | Polatuzumab vedotin Dose |
Peripheral neuropathy
| Grade 2 and 3 | Hold* If recovery in ≤14 days:
If recovery in >14 days:
|
Grade 4 | Discontinue | |
Neutropenia
| ≥ Grade 3 | Hold* Consider G-CSF for subsequent cycles. If recovery occurs in ≤7 days:
If recovery in >7 days:
|
Thrombocytopenia | ≥ Grade 3 | Hold* If recovery occurs in ≤7 days:
If recovery in >7 days:
|
Progressive multifocal leukoencephalopathy (PML) | Any | Hold and investigate; discontinue if confirmed. |
| Serious infections | Any | Discontinue |
*Do not retreat until ANC > 1 x 109/L, platelets > 75 x 109/L and peripheral neuropathy ≤ grade 1.
Management of Infusion-related Reactions:
Also refer to the CCO guideline for information on Management of Cancer Medication-Related Infusion Reactions.
Grade | Management | Re-challenge |
1-3 |
Restart:
|
|
4 |
|
|
Hepatic Impairment | Polatuzumab vedotin Dose (mg/kg) |
Total bilirubin ≤1.5 x ULN or AST/ALT ≤2.5 x ULN | No dose adjustment required |
Total bilirubin >1.5 x ULN or AST/ALT >2.5 x ULN | Avoid use. MMAE exposure may be increased and may lead to an increased incidence of adverse events. |
Renal Impairment | Polatuzumab vedotin Dose (mg/kg) |
Mild or moderate (CrCl ≥30 mL/min) | No dose adjustment required |
Severe (CrCl <30 mL/min) or ESRD | Has not been studied |
No dose adjustment required. Patients ≥ 65 of age had a higher incidence of ≥grade 3 adverse events and treatment discontinuation compared with younger patients.
Safety and efficacy in children have not been established.
DO NOT administer as an IV push or bolus.
Reconstitute using sterile water for injection, immediately before dilution.
Dilute in 0.9% sodium chloride, 0.45% sodium chloride or 5% dextrose IV infusion bag with a minimum volume of 50mL. Final concentration must be 0.72-2.7 mg/mL.
Do not shake vial or IV bag. Agitation can result in aggregation.
Infuse via dedicated line equipped with a sterile, non-pyrogenic, low-protein binding in-line or addon filter (0.2 or 0.22 µm size) and catheter.
Administration of Polatuzumab vedotin, bendamustine, and rituximab can occur any order on Day 1 of each cycle.
Initial dose should be administered over 90 minutes. If well tolerated, the subsequent doses may be administered over 30 minutes.
Patients should be monitored for infusion-related reactions during and for at least 90 minutes following the first infusion, and for at least 30 minutes following subsequent infusions.
If a polatuzumab vedotin dose is missed, administer as soon as possible. Adjust cycle schedule in order to maintain a 21-day interval between doses.
No incompatibilities have been observed between polatuzumab vedotin and:
IV infusion bags with polyvinyl chloride (PVC), or polyolefins (PO) such as polyethylene (PE) and polypropylene (PP).
Infusion sets or infusion aids with PVC, PE, polyurethane (PU), polybutadiene (PBD), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyetherurethane (PEU), or fluorinated ethylene propylene (FEP), or polytetrafluorethylene (PTFE).
Filter membranes composed of polyether sulfone (PES) or polysulfone (PSU).
- Store unopened vials at 2-8°C in the original carton to protect from light.
- Patients who have a hypersensitivity to this drug or any components of the formulation.
Other Warnings/Precautions:
- Patients with ≥ grade 2 peripheral neuropathy or prior allogeneic hematopoietic stem cell transplantation (HSCT) were excluded from clinical trials.
Ingestion of grapefruit, starfruit, Seville oranges, their juices or products while on polatuzumab therapy may increase MMAE plasma concentrations as these products have CYP3A4 inhibitory activity. Monitor closely for signs of toxicity.
Caution with driving or using machinery as peripheral neuropathy, fatigue, and dizziness may occur with treatment.
Other Drug Properties:
- Carcinogenicity: Unknown
Pregnancy and Lactation:
- Genotoxicity: Documented in animals
- Teratogenicity: Documented in animals
- Mutagenicity: No
- Embryotoxicity: Documented in animals
Polatuzumab is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 9 months after the last dose in females and for at least 6 months after the last dose in males.
- Breastfeeding:
Breastfeeding is not recommended during treatment and for at least 3 months after the last dose.
- Fertility effects: Documented in animals
Fertility may be impaired in males.
MMAE is a P-gp and CYP3A4/5 substrate and is a weak time-dependent inhibitor of CYP3A4/5. It does not competitively inhibit CYP3A4/5 or P-gp at clinically relevant concentrations.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Strong CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit) | ↑ polatuzumab vedotin exposure. (↑ AUC of unconjugated MMAE by 48%) | ↓ metabolism of polatuzumab vedotin | Monitor for signs of toxicities |
| Strong CYP3A4 inducers (i.e. phenytoin, rifampin, carbamazepine, phenobarbital, St. John’s Wort, etc) | ↓ polatuzumab vedotin concentration and/or efficacy. | ↑ metabolism of polatuzumab vedotin | Monitor for efficacy |
| Monitor Type | Monitor Frequency |
|---|---|
CBC | Baseline and before each cycle; consider more frequently for patients with Grade 3 or 4 neutropenia or thrombocytopenia |
Liver function tests | Baseline, before each cycle and as clinically indicated |
Renal function tests | Baseline, before each cycle and as clinically indicated |
Electrolytes, including sodium, potassium, magnesium and uric acid | Baseline and as clinically indicated |
Clinical toxicity assessment for infusion-related reactions, neuropathy, TLS, PML, bleeding, infection (including opportunistic), fatigue, and cardiovascular, nervous system, GI, or skin effects | As clinically indicated |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Polatuzumab Vedotin with Bendamustine and Rituximab (Biosimilar) - Relapsed or Refractory Diffuse Large B-cell Lymphoma
BC Cancer Protocol Summary for Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Not Eligible for Transplant using Polatuzumab Vedotin, Bendamustine and rituximab; April 2022.
Liebers N, Duell J, Fitzgerald D, et al. Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas. Blood Advances 2021;5(13):2707-2716
Product Monograph: Polivy (polatuzumab vedotin). Hoffman-La Roche Limited. Mississauga, Ontario. April 2021.
Prescribing Information: Polivy (polatuzumab vedotin). Genentech, Inc. South San Francisco, CA. September 2020.
Sehn L, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2019; 37. https://doi.org/10.1200/JCO.19.00172.
December 2022 Added indication in Dosing and Dose modifications sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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