Ofatumumab is a fully human monoclonal antibody directed against the CD20 molecule found on the surface of mature B-lymphocytes and some B-cell tumors. CD20 plays a role in the development and differentiation of B-cells, and monoclonal antibodies that target CD20 can cause the death of B-cells, making them useful in treating certain diseases characterized by excessive or abnormal B-cell activity.

Ofatumumab (Arzerra) is a human monoclonal antibody that targets CD-20 positive B lymphocytes and inhibits its activation.

Ofatumumab (Arzerra) Uses:

• Chronic lymphocytic leukemia, previously untreated:
  • When fludarabine-based therapy is considered inappropriate, treatment of previously untreated chronic lymphocytic leukemia (CLL) (in combination with chlorambucil)
• Chronic lymphocytic leukemia, relapsed:
  • Relapsed CLL treatment (in combination with fludarabine and cyclophosphamide).
• Chronic lymphocytic leukemia, refractory:
  • CLL Treatment  refractory to fludarabine & alemtuzumab
• Chronic lymphocytic leukemia, extended treatment:
  • After at least two lines of therapy for recurrent or progressive CLL, extended treatment of patients who are in complete or partial response

Ofatumumab (Arzerra) Dose in Adults

Note:

• Before you get treated with a medication (probably ofatumumab), your doctor may ask you to take acetaminophen (like Tylenol), an antihistamine (a drug that helps with allergies), and a corticosteroid (a type of medication) 30 to 120 minutes before your treatment.
• This is done to reduce the chances of certain side effects or allergic reactions when you receive the main treatment.

Ofatumumab (Arzerra) Dose in the treatment of Chronic lymphocytic leukemia (CLL), previously untreated:

• Cycle 1 (lasting 28 days):
  • Day 1: 300 mg given through an IV (a drip into your vein).
  • Day 8: 1,000 mg given through an IV.
• Every cycle after that (each cycle is 28 days):
  • Day 1: 1,000 mg given through an IV.
  • This goes on for at least 3 cycles. You can have up to 12 cycles in total. During this treatment, you'll also be given another drug called chlorambucil.

Getting Ready for the Treatment (Premedication):

• Before you get the Ofatumumab, take:
  • Acetaminophen (like Tylenol): 1,000 mg, by mouth.
  • An allergy medicine: Either 50 mg of diphenhydramine (like Benadryl) or 10 mg of cetirizine (like Zyrtec), by mouth or IV.
  • A steroid called prednisolone: 50 mg, through an IV.
• For the first two times you get Ofatumumab, you need the full dose of the steroid. If you don't have a bad reaction by the third time, your doctor might give you a lower dose or skip the steroid altogether.

Ofatumumab (Arzerra) Dose in the treatment of relapsed CLL:

• Cycle 1 (lasting 28 days):
  • Day 1: 300 mg given through an IV (a drip into your vein).
  • Day 8: 1,000 mg given through an IV.
• Every cycle after the first (each cycle is 28 days):
  • Day 1: 1,000 mg given through an IV.
  • This goes on for up to 6 cycles in total. During this treatment, you'll also be given two other drugs: fludarabine and cyclophosphamide.

Getting Ready for the Treatment (Premedication):

• Before you get the Ofatumumab, take:
  • Acetaminophen (like Tylenol): 1,000 mg, by mouth.
  • An allergy medicine: Either 50 mg of diphenhydramine (like Benadryl) or 10 mg of cetirizine (like Zyrtec), by mouth or IV.
  • A steroid called prednisolone: 50 mg, through an IV.
• For the first two times you get Ofatumumab, you should have the full dose of the steroid. But if you don't have a bad reaction after these, your doctor might lower the steroid dose or even skip it for the next treatments.

Ofatumumab (Arzerra) Dose in the treatment of refractory CLL:

• First Dose:
  • Day 1: 300 mg given through an IV.
• Weekly Doses (One week after the first dose):
  • You'll get 2,000 mg once a week. This happens 7 times (these are doses 2 to 8).
• Monthly Doses:
  • 4 weeks after your 8th dose, you'll get 2,000 mg. This happens once every 4 weeks for 4 times (these are doses 9 to 12). So, in total, you get 12 doses of the medicine.

Getting Ready for the Treatment (Premedication):

• Before you get the Ofatumumab, you should take:
  • Acetaminophen (like Tylenol): 1,000 mg, by mouth.
  • An allergy medicine: Like 50 mg of diphenhydramine (Benadryl) or 10 mg of cetirizine (Zyrtec), either by mouth or IV.
  • A steroid called prednisolone: 100 mg, through an IV.
• For the 1st, 2nd, and 9th doses of Ofatumumab, you'll need the full steroid dose.
• If you don't have a bad reaction after the first two doses, you might take a lower dose of the steroid or even skip it for doses 3 to 8.
• For doses 10 to 12, if you didn't have a bad reaction on the 9th dose, you'll take a reduced steroid dose (somewhere between half to the full 100 mg).

Ofatumumab (Arzerra) Dose in the treatment of CLL, extended:

• Start:
  • Day 1: Get 300 mg through an IV.
  • Day 8: Get 1,000 mg through an IV.
• Continued Doses:
  • 7 weeks after the Day 8 dose, you'll get 1,000 mg through an IV.
  • After that, you'll get 1,000 mg every 8 weeks.
  • You'll continue this for up to 2 years.

Getting Ready for the Treatment (Premedication):

• Before you get the Ofatumumab, you should take:
  • Acetaminophen (like Tylenol): 1,000 mg, by mouth.
  • An allergy medicine: Like 50 mg of diphenhydramine (Benadryl) or 10 mg of cetirizine (Zyrtec), either by mouth or IV.
  • A steroid called prednisolone: 50 mg, through an IV.
• For the first two times you get Ofatumumab, you'll need the full steroid dose.
• If you don't have a bad reaction after the first two doses, your doctor might lower the steroid dose or even skip it for the next treatments.

Ofatumumab use in children:

The safety and efficacy of the drug in children have not been established.

Ofatumumab Pregnancy Risk category: C

• Ofatumumab is a type of medicine made to act like a natural part of our immune system.
• When pregnant, medicines like this might move to the baby, especially as the pregnancy goes on.
• The risk is lowest when the baby's organs are forming.
• Animal studies show that ofatumumab can decrease certain immune cells (B cells) for a long time.
• So, if a baby was exposed to ofatumumab before birth, it's best not to give them live vaccines until their B cells are back to normal.

Use of Ofatumumab while breastfeeding

• Ofatumumab might be found in breast milk because similar substances (human IgG) are found in it.
• Even though antibodies from breast milk usually don't get into a baby's blood in large amounts, it's not fully clear with ofatumumab.
• So, if a mom is taking ofatumumab and wants to breastfeed, she should weigh the possible risks to her baby against the health benefits she gets from the medicine.
• The drug company recommends thinking about both when deciding whether to breastfeed.

Ofatumumab Dose in Kidney Disease:

• If your kidneys filter out 30 mL or more of waste per minute (CrCl ≥30 mL/minute), the US drug maker doesn't suggest changing the dose of the medicine. Studies have shown that the medicine works the same way in people with this kidney function.
• If your kidneys filter out less than 30 mL of waste per minute (CrCl <30 mL/minute), the drug maker hasn't given any advice on dosing. They haven't studied it in people with this level of kidney function.

Ofatumumab Dose in Liver Disease:

• The drug maker hasn't given any guidance on changing the dose for people with kidney problems.
• They haven't studied the medicine in this group of people.

Common Side Effects of Ofatumumab (Arzerra):

• Central Nervous System:
  • Fatigue
• Dermatologic:
  • Skin Rash
• Gastrointestinal:
  • Diarrhea
  • Nausea
• Hematologic & Oncologic:
  • Neutropenia
  • Anemia
• Infection:
  • Infection
  • Serious Infection
• Respiratory:
  • Pneumonia
  • Cough
  • Upper Respiratory Tract Infection
  • Dyspnea
  • Bronchitis
• Miscellaneous:
  • Infusion Related Reaction
  • Fever

Less Common Side Effects Of Ofatumumab (Arzerra):

• Cardiovascular:
  • Peripheral Edema
  • Hypertension
  • Hypotension
  • Tachycardia
• Central Nervous System:
  • Chills
  • Insomnia
  • Headache
• Dermatologic:
  • Urticaria
  • Hyperhidrosis
• Hematologic & Oncologic:
  • Hypogammaglobulinemia
• Infection:
  • Sepsis
  • Influenza
  • Herpes Zoster
• Neuromuscular & Skeletal:
  • Back Pain
  • Muscle Spasm
• Respiratory:
  • Nasopharyngitis
  • Sinusitis

Contraindications to Ofatumumab (Arzerra):

The U.S. instructions from the drug maker don't list any situations where you shouldn't use the medicine.

But in Canada, they say don't use it if you're allergic to ofatumumab or any part of the drug, or if you have or had a brain disease called progressive multifocal leukoencephalopathy.

Warnings and precautions

Hematologic toxicities:

• Taking this medicine can lead to very low blood cell counts, which might last for more than a week.
• This includes low white blood cells (which fight infections), low platelets (which help blood clot), and low red blood cells (which carry oxygen).
• There have been cases where low white blood cell counts started long after the last dose of the medicine.
• Some people, especially when also taking a drug called chlorambucil, had dangerously low blood counts or even died from infections due to very few white blood cells.
• It's crucial to check blood levels often during and after treatment, and even more often if the blood cell counts drop a lot.

Hepatitis B virus infection: [US Boxed Warn]

• When people receive treatments like ofatumumab, there's a risk that a virus called hepatitis B can become active again in their body.
• This can lead to severe liver problems, even death.
• It can happen even if they didn't have hepatitis B before.
• So, before starting this treatment, doctors need to check if the patient has any signs of hepatitis B.
• They also need to keep an eye on the patient's liver during and after the treatment.
• If hepatitis B becomes active, the treatment should be stopped, and the patient should get medicine to treat the hepatitis B.
• People who have had hepatitis B in the past or who are at high risk of getting it should also be watched carefully and may need to take medicine to prevent it from becoming active again.
• This is really important because reactivation of hepatitis B can happen even after the treatment has stopped.
• So, doctors need to be cautious and take steps to protect the patient's liver.

Infection

• While on the treatment and even after it's done, there's a chance of getting bacterial, fungal, or viral infections, or having old infections come back.
• So, it's important to watch for any signs of infections and get them checked out.

Infusion reaction

• Getting the treatment might cause some serious reactions during the infusion.
• These reactions can include breathing problems, heart issues, back or stomach pain, fever, skin reactions, and even severe allergic reactions.
• These reactions are more common during the first two treatments, even if you take other medications to prevent them.
• Before getting the treatment, you'll be given medicines like acetaminophen, an allergy medicine, and a steroid to help reduce the chance of a reaction.
• If you have a reaction during the infusion, the treatment might be paused or given more slowly.
• If you have a severe allergic reaction, the treatment will be stopped for good.

Progressive multifocal Leukoencephalopathy: [US-Bound Warning]

• There's a serious warning that taking medicines like ofatumumab can cause a dangerous brain condition called Progressive Multifocal Leukoencephalopathy (PML), which can lead to death.
• If someone starts having new or worsening brain or nerve symptoms while on this treatment, doctors should think about PML as a cause.
• If they suspect PML, the treatment with ofatumumab should be stopped and the patient should be checked quickly.

Tumor lysis syndrome

• Taking ofatumumab can lead to a condition called Tumor Lysis Syndrome (TLS).
• This happens when lots of cancer cells die at once, releasing their contents into the bloodstream.
• People with a lot of cancer cells, especially if they have high numbers of a specific type of blood cell, are more at risk.
• To help prevent TLS, patients should be given medicine to reduce uric acid levels and plenty of fluids, starting 12 to 24 hours before getting ofatumumab.
• It's also important to make sure the body's salt levels are balanced and to keep an eye on kidney function and hydration.

Ofatumumab: Drug Interaction

Monitoring Parameters:

Blood Checks:

• Complete blood count (CBC) with details:
  • Regularly during and after therapy.
  • Even more often if serious blood cell drop happens.

Kidney and Salt Levels:

• Check kidney function.
• Monitor salt levels in the blood.

Hepatitis B Screening (Based on ASCO advice [Hwang 2015]):

• Before starting treatment, test for Hepatitis B using:
  • Hepatitis B surface antigen (HBsAg).
  • Hepatitis B core antibody (anti-HBc). Use the version with both IgG and IgM or just the IgG. Don't use just the IgM as it might only show a fresh infection.
• If the HBsAg test is negative but the anti-HBc test is positive:
  • Regularly check for Hepatitis B reactivation using HBV DNA and ALT tests, about every 3 months during treatment.

Symptoms to Watch Out For

• Liver Issues:
  • Signs of active Hepatitis B, during treatment and for up to a year after.
  • Any hepatitis symptoms.
• During Infusion:
  • Any signs or feelings that something is wrong during the drip (infusion reaction).
• General Health:
  • Any signs of infection.
  • Check fluid levels in the body.
• Stomach Issues:
  • Stomach pain or throwing up multiple times. This could be a blockage in the gut.
• Brain Concerns:
  • Watch for signs of a brain condition called Progressive Multifocal Leukoencephalopathy. This might look like weakness on one side of the body, vision problems, trouble thinking, speaking issues, coordination problems, or issues with face muscles.

How to administer Ofatumumab (Arzerra)?

General Instructions:

• Do not give it quickly (push), as a bolus, or as an injection under the skin.
• Give pre-medicines like acetaminophen, an antihistamine, and a corticosteroid between 30 minutes to 2 hours before starting.
• Make sure you're in a place where any reaction to the infusion can be quickly dealt with.
• Use an infusion pump and a specific set for administering.
• Follow the given rates. Don't mix this medicine with others.
• Rinse (flush) the IV line with saline solution before and after giving ofatumumab.
• Start the infusion within 12 hours after you prepare it.
• If there's a bad reaction during the infusion, stop it. You can start again later at a slower rate if the reaction wasn't too severe (details in the Dosage Adjustment for Toxicity section).

For Patients with CLL (various stages):

• First 300 mg dose:
  • Start at 12 mL/hour for 30 minutes.
  • Then increase the speed step by step if the patient is okay: 25, 50, 100, 200, 300, and finally 400 mL/hour. The full infusion usually takes about 5 hours.
• Later 1,000 mg doses (if the first one was okay):
  • Start at 25 mL/hour for 30 minutes.
  • Increase as before: 50, 100, 200, and then 400 mL/hour. This takes around 4.5 hours.

For Patients with Hard-to-Treat CLL (Refractory CLL):

• First and Second Doses:
  • Start at 12 mL/hour for 30 minutes.
  • Increase step by step: 25, 50, 100, and then 200 mL/hour. It'll take about 7 hours.
• Doses from the 3rd to 12th (if previous ones were okay):
  • Start at 25 mL/hour for 30 minutes.
  • Increase as before: 50, 100, 200, and then 400 mL/hour. Again, around 4.5 hours in total.

Mechanism of action of Ofatumumab (Arzerra):

• Ofatumumab is a specially designed antibody.
• It sticks to a specific part of the CD20 molecule found on certain cells, especially B lymphocytes (a type of white blood cell) and in a condition called B-cell CLL.
• When it binds to these cells, it helps the immune system destroy them through two main methods: making the cell burst open or using other cells to kill the targeted cell.
• This is especially useful for cells that have too much CD20 on their surface.

How it spreads in the body:

• Ofatumumab has a volume of distribution of 6.1 liters after being given multiple times, meaning it spreads to that much body fluid.

How long it stays in the body:

• After being given multiple times, it takes about 17.6 days for half of the ofatumumab to be removed from the body.

International Brands of Ofatumumab:

• Arzerra

Ofatumumab Brand Names in Pakistan:

Not available.