Polatuzumab vedotin is an antibody-drug conjugate used in the treatment of cancer, particularly in certain types of non-Hodgkin lymphoma (NHL). The drug specifically targets CD79b, a protein that is abundantly expressed on the surface of most B-cell malignancies.

Polatuzumab vedotin (Polivy) is an antibody-drug conjugate (ADC) that causes cell-cycle arrest and induces apoptosis. It has got FDA approval for the treatment of patients with diffuse large B-cell lymphoma in combination with Rituximab and Bendamustine.

Polatuzumab vedotin (Polivy) Uses:

• Diffuse large B-cell lymphoma (relapsed or refractory):
  • Treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (in combination with bendamustine and a rituximab product) not otherwise specified, after at least two prior therapies.

Polatuzumab vedotin (Polivy) Dose in Adults

When someone is getting treated with polatuzumab vedotin:

• Give them protection against a type of pneumonia (caused by Pneumocystis jiroveci) and certain herpes viruses the entire time they're on the treatment.
• If they haven't already gotten it, give them medicine to prevent allergies and fever about 30 to 60 minutes before they get the polatuzumab vedotin.
• Think about giving them something to boost their blood cell growth.
• Give them protection against a condition called tumor lysis syndrome if the doctor thinks it's needed.

Polatuzumab vedotin (Polivy) Dose in the treatment of Relapsed or Refractory Diffuse large B-cell Lymphoma:

In treating Diffuse Large B-cell Lymphoma that has come back or not responded well to treatment:

• The medicine is given through a vein (IV).
• The dose is based on the person's weight: 1.8 mg of the medicine per kilogram (kg) of their weight.
• This is given once every 21 days, and they'll have a total of 6 cycles of treatment.
• It's used along with two other medicines: bendamustine and rituximab.

If a dose is missed:

• Give the missed dose as soon as possible.
• Adjust the treatment schedule to keep a gap of 21 days between doses.

Use in Children:

Not indicated.   

Pregnancy Risk Category: N

Because of how polatuzumab vedotin works and the results from studies on animals:

• If a pregnant person is exposed to polatuzumab vedotin while pregnant, it could harm the developing baby.
• Before using polatuzumab vedotin, doctors should check if a woman can become pregnant to make sure she's not already pregnant.
• Women who can become pregnant should use effective birth control while getting this treatment and for at least 3 months after the last dose of polatuzumab vedotin.
• Men who are getting this treatment and have female partners who could become pregnant should also use effective birth control. This should continue during the treatment and for at least 5 months after the last dose of polatuzumab vedotin.

The goal is to prevent any possible harm to the fetus during and after the treatment.

Use of Polatuzumab vedotin during breastfeeding

• We don't know if polatuzumab vedotin can be found in breast milk.
• Because there's a risk that it could seriously harm a baby who's being breastfed, the company that makes the medicine advises against breastfeeding.
• If someone's taking this medicine, they should not breastfeed during the treatment and for at least 2 months after they take the last dose.

Polatuzumab vedotin (Polivy) Dose in Kidney Disease:

CrCl is a measure of kidney function, specifically how efficiently the kidneys filter the blood.

• For people with a CrCl between 30 and 89 mL/minute:
  • The company that makes the medicine hasn't given any guidance about changing the dose.
  • Studies show that, within this range of kidney function, there aren't any major changes in how the body handles the medicine.
• For people with a CrCl below 30 mL/minute:
  • The company hasn't provided guidance on changing the dose because they haven't studied this group of people.
• For people with end-stage renal disease (serious kidney issues, whether or not they're on dialysis):
  • The company hasn't provided guidance on changing the dose because they haven't studied this situation.

This means, for certain levels of kidney function, it's not clear if the medicine's dosage should be adjusted.

Polatuzumab vedotin (Polivy) Dose in Liver disease:

• AST and ALT are enzymes found in the liver. When their levels are high, it suggests the liver might be injured or not working properly.
• ULN stands for "Upper Limit of Normal". It's the highest amount you'd expect to see in a healthy person.

• Mild liver impairment:
  • If AST or ALT levels are a little high (more than the normal limit but up to 2.5 times that limit) OR
  • If total bilirubin (another liver marker) is slightly high (more than the normal limit but up to 1.5 times that limit):
    • The person can take the medicine without any changes to the usual dose.
• Moderate to severe liver impairment:
  • If AST or ALT levels are significantly high (more than 2.5 times the normal limit) OR
  • If total bilirubin is much higher (more than 1.5 times the normal limit):
    • It's better to avoid the medicine.
    • The reason is that the active part of the medicine (called monomethylauristatin E) might stay in the body longer or be more concentrated in people with these liver issues, which can be risky.

Common Side Effects of Polatuzumab vedotin (Polivy):

• Central Nervous System:
  • Dizziness
  • Peripheral Neuropathy
• Endocrine & Metabolic:
  • Decreased Serum Calcium
  • Hypokalemia
  • Weight Loss
  • Hypoalbuminemia
  • Hypocalcemia
• Gastrointestinal:
  • Diarrhea
  • Increased Serum Lipase
  • Decreased Appetite
  • Increased Serum Amylase
  • Vomiting
• Hematologic & Oncologic:
  • Neutropenia
  • Thrombocytopenia
  • Anemia
  • Lymphocytopenia
  • Febrile Neutropenia
• Hepatic:
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Transaminase
• Renal:
  • Increased Serum Creatinine
• Respiratory:
  • Pneumonia
  • Upper Respiratory Tract Infection
• Miscellaneous:
  • Fever
  • Infusion Related Reaction

Less Common Side Effects Of Polatuzumab vedotin (Polivy):

• Endocrine & Metabolic:
  • Hypophosphatemia
• Hematologic & Oncologic:
  • Pancytopenia
• Hepatic:
  • Increased Serum Transaminases
  • Hepatotoxicity
• Immunologic:
  • Antibody Development
• Infection:
  • Sepsis
• Neuromuscular & Skeletal:
  • Arthralgia
• Respiratory:
  • Pneumonitis

Polatuzumab vedotin (Polivy) Side effects (Frequency Not Defined):

• Hepatic:
  • Increased Serum Bilirubin
• Infection:
  • Cytomegalovirus Disease
  • Herpes Virus Infection
• Respiratory:
  • Pneumonia Due To Pneumocystis Jirovecii

Contraindications to Polatuzumab vedotin (Polivy):

The company that makes the medicine hasn't listed any situations where it's definitely unsafe or not recommended to use the medicine.

Warnings and precautions

Suppression of bone marrow

• During polatuzumab vedotin treatment, there can be a significant decrease in bone marrow function, leading to serious low blood cell counts.
• This might result in severe neutropenia, thrombocytopenia, anemia, and lymphopenia, sometimes causing fever due to low neutrophil levels.
• More than 40% of patients used a medication to help prevent this.
• Keep an eye on blood counts while on treatment; if this issue occurs, it might be necessary to pause treatment, lower the dose, or stop altogether.
• Using medications to boost blood cell production could also be considered.

Hepatotoxicity

• Taking polatuzumab vedotin can cause serious liver problems.
• Some people have shown signs of liver damage, with increased levels of certain liver enzymes and/or bilirubin.
• While only a few had very high enzyme levels, there were instances where the drug likely caused liver injury.
• Those with existing liver issues, already high liver enzyme levels, or taking other medications that can harm the liver might be at a higher risk.
• It's essential to regularly check liver enzyme levels and bilirubin to catch any problems early on.

Infection

• Taking polatuzumab vedotin can lead to serious or even deadly infections, including rare types of pneumonia and viruses like herpes.
• It's crucial to watch closely for any signs of these infections.
• To help prevent certain infections, protection against the P.
• jiroveci pneumonia and herpes virus is needed while on this treatment.
• Nearly one in three patients had severe infections, and a small number sadly passed away due to infections within 90 days after their last dose.

Reactions that are related to infusion:

• Taking polatuzumab vedotin can sometimes cause reactions during or after it's given into the vein.
• Some people experienced symptoms like fever, chills, redness, difficulty breathing, low blood pressure, and hives.
• Most of these reactions were mild or moderate.
• Even though the medicine is given right away, some reactions can happen up to 24 hours later.
• It's important to watch patients during and after they get the medication.
• To help prevent these reactions, patients should be given an allergy medicine and fever reducer before getting polatuzumab vedotin.
• If someone does have a reaction, the infusion should be paused, and they should get medical care right away.

Peripheral neuropathy

• Polatuzumab vedotin can cause nerve problems, often called peripheral neuropathy.
• This issue can build up over time and can make any existing nerve problems worse.
• Some people can feel these nerve changes as early as their first treatment.
• Most of the time, it affects feeling (like numbness or tingling) but can also affect movement.
• Most cases are mild or moderate, but some can be severe.
• On average, people noticed these nerve issues about 2 months into treatment.
• The good news is that for about half of the patients, the nerve problems went away entirely, and for almost two-thirds, they got better or disappeared after about a month.
• It's crucial to watch for symptoms like numbness, tingling, pain, a burning feeling, weakness, or trouble walking.
• If these symptoms appear or get worse, it might be necessary to pause the treatment, lower the dose, or stop it altogether.

Progressive multifocal Leukoencephalopathy

• Polatuzumab vedotin can sometimes cause a rare brain infection called progressive multifocal leukoencephalopathy (PML).
• It's vital to watch out for new or worsening brain-related symptoms, like changes in thinking, behavior, or physical abilities.
• If someone shows signs that might suggest PML while on the treatment, doctors should pause both polatuzumab vedotin and any other chemotherapy they're on.
• If tests confirm they have PML, then polatuzumab vedotin should be stopped for good.

Tumor lysis syndrome

• Polatuzumab vedotin can sometimes cause a condition called tumor lysis syndrome (TLS).
• This happens when cancer cells break down rapidly, releasing their contents into the bloodstream.
• Patients who have a lot of cancer cells or whose cancer is growing quickly are at a higher risk.
• It's important to keep a close eye on patients for signs of TLS.
• If needed, doctors should give treatments to prevent or manage TLS based on the patient's condition.

Hepatic impairment

• People with moderate to severe liver problems shouldn't take polatuzumab vedotin.
• One of the parts of this drug, called monomethylauristatin E (MMAE), might stay in their system longer, which can lead to more side effects.
• So, it's best to avoid using this medicine in those with notable liver issues to prevent potential complications.

Polatuzumab vedotin: Drug Interaction

Risk Factor C (Monitor therapy)
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

Monitoring parameters:

Blood Checks:

• Check complete blood count (CBC) regularly during treatment.
• Conduct liver function tests.

Before Starting Treatment:

• Take a pregnancy test for women who might become pregnant.

During Infusions:

• Watch patients for at least 90 minutes after the first dose and at least 30 minutes after later doses for reactions.

What to Look Out For:

• Nerve Issues: Symptoms like numbness, tingling, burning, pain, weakness, or problems walking.
• Tumor Breakdown (Tumor Lysis Syndrome): A rapid release of cell contents.
• Brain Infection (Progressive Multifocal Leukoencephalopathy): Watch for new or worsening brain symptoms.
• Infections: Look out for signs of any infections.

How to administer Polatuzumab vedotin (Polivy)?

First Dose:

• Infuse over 90 minutes.
• Use a special infusion line with a specific filter (0.2 or 0.22-micron).
• Watch the patient for at least 90 minutes after the infusion ends for any reactions.

Next Doses:

• If the first dose goes well, the next ones can be given over 30 minutes.
• After the infusion, monitor the patient for at least 30 minutes.

Before Infusion:

• Give an allergy medicine (antihistamine) and a fever reducer (antipyretic) 30 to 60 minutes before each dose.

If There's a Reaction:

• Stop the infusion right away and give necessary supportive treatment.
• When the reaction stops, start the infusion again but at half the previous rate.
• If the patient is okay with the slower rate, you can increase the speed gradually by 50 mg/hour every 30 minutes.
• For dose changes due to reactions, see the specific guidance under "Dosing: Adjustment for Toxicity."

Giving with Other Medicines:

• You can give polatuzumab vedotin, bendamustine, and rituximab in any order on the first day of each treatment cycle.
• Don't give it as a quick push or all at once, and don't mix or give it with other meds at the same time.

Mechanism of action of Polatuzumab vedotin (Polivy):

Polatuzumab vedotin is a type of medicine called an antibody-drug conjugate (ADC). It's designed to target a protein called CD79b, found on the surface of certain B-cells, which are a type of white blood cell. This medicine has three main parts:

• Antibody: This is like a scout that searches for CD79b. It's a humanized antibody, which means it's a type of protein created to be similar to the ones our body naturally produces to fight off infections.
• Molecule that Destroys Microtubules: Attached to the antibody is a molecule called monomethylauristatin E (MMAE). This molecule is like a tiny "bomb" that can disrupt the cells' internal structures, specifically the microtubules.
• Linker: The MMAE is connected to the antibody using a special linker. This is like the string holding the "bomb" to the antibody.

When the ADC is given to a person, the antibody part homes in on the CD79b protein on the cancerous B-cells. It forms a complex with the cells, gets inside, and releases the MMAE "bomb." This bomb then attaches to the cell's internal structures called microtubules, causing them to break down. This disruption stops the cell from growing and dividing (it's like hitting the brakes on the cell cycle). Ultimately, this process leads to cell death.

This is how polatuzumab vedotin works to target and destroy certain cancerous B-cells by specifically attacking the CD79b protein on their surface.

How it Spreads in the Body:

• Volume of Distribution (V): The part of the drug that's attached to the antibody (called antibody-conjugated MMAE) spreads out to about 3.15 liters in the body.

How it Binds to Proteins:

• Protein Binding: MMAE binds to proteins in the body at a rate of 71% to 77%.

How it's Processed (Metabolism):

• MMAE gets broken down into smaller parts like peptides, amino acids, and other smaller components. Also, it gets detached (or unconjugated) from the main drug.
• MMAE is processed in the liver by an enzyme called CYP3A4.

How Long it Stays in the Body (Half-life):

• Antibody-conjugated MMAE: It takes around 12 days (by the 6th cycle of treatment) for half of this component to be cleared out from the body.
• Unconjugated MMAE: It takes about 4 days (after the first dose) for half of this component to be cleared out.

How it's Removed from the Body (Excretion):

• Clearance: The body clears out the antibody-conjugated MMAE at a rate of about 0.9 liters per day.

International Brand Names of Polatuzumab vedotin:

• Polivy

Polatuzumab vedotin Brand Names in Pakistan:

Not Available.