Drugs List

Therapeutic Indications

Uses

Large B-cell lymphoma

Treatment in combination with bendamustine and rituximab of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) for whom haematopoietic stem cell transplant is not suitable.

Administration

Polatuzumab vedotin is for intravenous use.

Polatuzumab vedotin should not be administered as intravenous push or bolus.

Contraindications

Children under 18 years
Severe infection
Breastfeeding
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute

Precautions and Warnings

Females of childbearing potential
Dehydration
Hepatic disorder
Peripheral neuropathy
Positive HIV status

Administration of live vaccines is not recommended
Appropriate antibiotic therapy required in presence or if risk of infection
Consider pre-medication with antihistamines and/or antipyretics
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Prophylactic G-CSF should be considered
Concentrate must be diluted and used as an infusion
Consult local policy on the safe use of anti-cancer drugs
Do not mix with other drugs or substances
For single use only
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Staff: Not to be handled by pregnant staff
Treatment to be administered under the supervision of a specialist
Exclude pregnancy prior to initiation of treatment
May cause activation / exacerbation of latent / intercurrent infections
Monitor closely any patient who develops new infection while on treatment
Monitor complete blood counts before each dose
Monitor for symptoms of peripheral neuropathy
Monitor levels of hepatic enzymes and bilirubin
Monitor patient closely for serious adverse events following administration
Monitor patients for signs of tumour lysis syndrome
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider discontinuing treatment if serious infection occurs
Consider dose reduction/stopping if new/worsening peripheral neuropathy
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue permanently if life threatening infusion reactions occur
Interrupt treatment if severe infusion reaction occurs
Suspend treatment and/or reduce dose for grade 3 thrombocytopenia
Suspend treatment if grade 3 neutropenia occurs
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 9 months after treatment
Male: Contraception required during and for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 3 months after treatment
Driving or operating machinery not advisable following treatment

Infusion-related reactions (IRR)
The initial dose of polatuzumab vedotin should be administered as a 90-minute intravenous infusion. Patients should be monitored for infusion-related and hypersensitivity reactions during the infusion and for at least 90 minutes following completion of the initial dose.

Discontinue permanently infusion if first time in presence of wheezing, bronchospasm and generalized urticaria (Grade 3 reactions). Also, discontinue permanently in case of recurrent Grade 2 wheezing and urticaria or any other recurrent Grade 3 symptoms.

Infusion may be restarted at 50% of the rate achieved prior to interruption in cases of complete resolution of symptoms. In the absence of infusion-related symptoms, the rate of infusion may be escalated in increments of 50mg/hour.

If the initial infusion was well tolerated, the subsequent dose of polatuzumab vedotin 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. Administer premedication for all cycles.

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. Polatuzumab vedotin and any concomitant chemotherapy should be withheld if PML is suspected. If PML is diagnosed, treatment should be permanently discontinued.

Tumour lysis syndrome (TLS)
Patients with high tumour burden and rapidly proliferative tumour may be at increased risk of TLS. Appropriate measures and prophylaxis in accordance with local guidelines should be taken prior to treatment with polatuzumab vedotin.

Pregnancy and Lactation

Pregnancy

Polatuzumab vedotin is contraindicated during pregnancy.

The manufacturer does not recommend the use of polatuzumab vedotin during pregnancy and in women of childbearing potential not using contraception unless the potential benefit outweighs the potential risk to the foetus.

There are no data in pregnant women using polatuzumab vedotin. Animal studies have shown reproductive toxicity. Based on the mechanism of action and nonclinical studies, polatuzumab vedotin can be harmful to the foetus when administered to a pregnant woman.

Lactation

Polatuzumab vedotin is contraindicated during breastfeeding.

The manufacturer recommends discontinuing breastfeeding during treatment with polatuzumab vedotin for at least 3 months after the last dose.

It is not known whether polatuzumab vedotin or its metabolites are excreted in human breast milk. A risk for breast feeding children cannot be excluded.

Side Effects

Abdominal pain
Anaemia
Arthralgia
Asthenia
Blurred vision
Chills
Constipation
Cough
Cytomegalovirus infection
Decreased appetite
Diarrhoea
Dizziness
Elevated serum lipase
Fatigue
Febrile neutropenia
Gait abnormality
Herpes infections
Hyperbilirubinaemia
Hypoaesthesia
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hypophosphataemia
Increase of liver transaminases
Infertility
Infusion-related symptoms
Leukopenia
Lymphopenia
Nausea
Neutropenia
Pancytopenia
Paraesthesia
Peripheral neuropathy
Peripheral sensory neuropathy
Pneumonia
Pneumonitis
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pyrexia
Sepsis
Thrombocytopenia
Tumour lysis syndrome
Upper abdominal pain
Upper respiratory tract infection
Vomiting
Weight loss

Presentation

Infusions of polatuzumab vedotin.

These products have been produced by recombinant technology using Chinese Hamster Ovary (CHO) cell lines.

Drugs List

Therapeutic Indications

Uses

Large B-cell lymphoma

Treatment in combination with bendamustine and rituximab of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) for whom haematopoietic stem cell transplant is not suitable.

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Additional Dosage Information

Administration

Polatuzumab vedotin is for intravenous use.

Polatuzumab vedotin should not be administered as intravenous push or bolus.

Contraindications

Children under 18 years
Severe infection
Breastfeeding
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute

Precautions and Warnings

Females of childbearing potential
Dehydration
Hepatic disorder
Peripheral neuropathy
Positive HIV status

Administration of live vaccines is not recommended
Appropriate antibiotic therapy required in presence or if risk of infection
Consider pre-medication with antihistamines and/or antipyretics
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Prophylactic G-CSF should be considered
Concentrate must be diluted and used as an infusion
Consult local policy on the safe use of anti-cancer drugs
Do not mix with other drugs or substances
For single use only
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Staff: Not to be handled by pregnant staff
Treatment to be administered under the supervision of a specialist
Exclude pregnancy prior to initiation of treatment
May cause activation / exacerbation of latent / intercurrent infections
Monitor closely any patient who develops new infection while on treatment
Monitor complete blood counts before each dose
Monitor for symptoms of peripheral neuropathy
Monitor levels of hepatic enzymes and bilirubin
Monitor patient closely for serious adverse events following administration
Monitor patients for signs of tumour lysis syndrome
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider discontinuing treatment if serious infection occurs
Consider dose reduction/stopping if new/worsening peripheral neuropathy
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue permanently if life threatening infusion reactions occur
Interrupt treatment if severe infusion reaction occurs
Suspend treatment and/or reduce dose for grade 3 thrombocytopenia
Suspend treatment if grade 3 neutropenia occurs
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 9 months after treatment
Male: Contraception required during and for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 3 months after treatment
Driving or operating machinery not advisable following treatment

Infusion-related reactions (IRR)
The initial dose of polatuzumab vedotin should be administered as a 90-minute intravenous infusion. Patients should be monitored for infusion-related and hypersensitivity reactions during the infusion and for at least 90 minutes following completion of the initial dose.

Discontinue permanently infusion if first time in presence of wheezing, bronchospasm and generalized urticaria (Grade 3 reactions). Also, discontinue permanently in case of recurrent Grade 2 wheezing and urticaria or any other recurrent Grade 3 symptoms.

Infusion may be restarted at 50% of the rate achieved prior to interruption in cases of complete resolution of symptoms. In the absence of infusion-related symptoms, the rate of infusion may be escalated in increments of 50mg/hour.

If the initial infusion was well tolerated, the subsequent dose of polatuzumab vedotin 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. Administer premedication for all cycles.

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. Polatuzumab vedotin and any concomitant chemotherapy should be withheld if PML is suspected. If PML is diagnosed, treatment should be permanently discontinued.

Tumour lysis syndrome (TLS)
Patients with high tumour burden and rapidly proliferative tumour may be at increased risk of TLS. Appropriate measures and prophylaxis in accordance with local guidelines should be taken prior to treatment with polatuzumab vedotin.

Pregnancy and Lactation

Pregnancy

Polatuzumab vedotin is contraindicated during pregnancy.

The manufacturer does not recommend the use of polatuzumab vedotin during pregnancy and in women of childbearing potential not using contraception unless the potential benefit outweighs the potential risk to the foetus.

There are no data in pregnant women using polatuzumab vedotin. Animal studies have shown reproductive toxicity. Based on the mechanism of action and nonclinical studies, polatuzumab vedotin can be harmful to the foetus when administered to a pregnant woman.

Lactation

Polatuzumab vedotin is contraindicated during breastfeeding.

The manufacturer recommends discontinuing breastfeeding during treatment with polatuzumab vedotin for at least 3 months after the last dose.

It is not known whether polatuzumab vedotin or its metabolites are excreted in human breast milk. A risk for breast feeding children cannot be excluded.

Side Effects

Abdominal pain
Anaemia
Arthralgia
Asthenia
Blurred vision
Chills
Constipation
Cough
Cytomegalovirus infection
Decreased appetite
Diarrhoea
Dizziness
Elevated serum lipase
Fatigue
Febrile neutropenia
Gait abnormality
Herpes infections
Hyperbilirubinaemia
Hypoaesthesia
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hypophosphataemia
Increase of liver transaminases
Infertility
Infusion-related symptoms
Leukopenia
Lymphopenia
Nausea
Neutropenia
Pancytopenia
Paraesthesia
Peripheral neuropathy
Peripheral sensory neuropathy
Pneumonia
Pneumonitis
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pyrexia
Sepsis
Thrombocytopenia
Tumour lysis syndrome
Upper abdominal pain
Upper respiratory tract infection
Vomiting
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2021

Reference Sources

Summary of Product Characteristics: Polivy 140mg powder for concentrate for solution for infusion. Roche Products Limited. Revised December 2020.

Summary of Product Characteristics: Polivy 30mg powder for concentrate for solution for infusion. Roche Products Limited. Revised December 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 March 2021