What Are PI3K Inhibitors?

These medicines focus on the B cells in your immune system. B cells are a special type of white blood cell that normally protect against infection. If you have chronic lymphocytic leukemia (CLL), your B cells change and become cancerous. 

When it comes to CLL, your doctor might suggest a phosphatidylinositol 3-kinase (PI3K) inhibitor. These medicines block signals that prompt cancer cells to multiply. But they can cause serious side effects. For that reason, PI3K inhibitors are generally only used for CLL when other treatments fail. 

How Do PI3K Inhibitors Work?

PI3K inhibitors block the PI3K enzyme, which is important for B-cell survival. By blocking PI3K, these drugs can help control overactive, cancerous B cells. This process may slow the growth and spread of cancer cells.   

Which PI3K Inhibitors Are Used to Treat CLL?

When Are PI3K Inhibitors Used to Treat CLL?

PI3K inhibitors are not considered first-line treatments. That means they won’t be the first medicine your doctor suggests.

Duvelisib may be given to adults with CLL who have tried at least two other therapies that didn’t work or no longer work. 

Idelalisib is used along with another medicine called rituximab (Rituxan). It’s an option for people with relapsed CLL, which means your cancer comes back after you have had other treatments. 

How Do You Take PI3K Inhibitors?

They come as a pill that you take by mouth.

Duvelisib is a capsule that you take twice a day at the same times. It can be used with or without food. 

Idelalisib comes as a tablet. You also take this medicine twice a day at the same times, with or without food.

How long do you take PI3K inhibitors?

The length of time you’ll take a PI3K inhibitor depends on how you respond and tolerate it. If you have a bad reaction or severe side effects, your doctor might bump down your dose. In some cases, they may tell you to stop the drug for a while, or for good. 

THUMBNAIL, Serious Side Effects of PI3K Inhibitors infographic

How Effective Are PI3K Inhibitors?

These medicines have been proven to be effective in studies. 

Are PI3K Inhibitors Safe?

These medicines can cause life-threatening side effects and complications. For this reason, doctors typically only use them when other, less-toxic medicines fail. 

Idelalisib

The company that manufactures idelalisib warns that the medicine can cause serious side effects that could lead to death. 

Idelalisib has a boxed warning to let patients know that it could cause:

  • Serious or life-threatening liver damage 
  • Severe diarrhea or colitis (swelling of your colon)
  • Tears in your intestines
  • Pneumonitis (swelling of your lungs)
  • Serious or life-threatening infections 

Duvelisib

In studies, 15% of people who took duvelisib died from treatment-related problems. Infections were the most common reason for treatment-related deaths.

Duvelisib has a boxed warning to let patients know that it could cause:

  • Serious or life-threatening infections
  • Severe diarrhea or colitis
  • Serious or life-threatening skin reactions 
  • Pneumonitis 

What Are the Common Side Effects of PI3K Inhibitors?

Like all medicines, PI3K Inhibitors can cause side effects. You should let your doctor know if these issues become serious or don’t go away. 

Duvelisib 

Some common side effects of duvelisib are:

  • Diarrhea
  • Cough
  • Fever
  • Extreme tiredness (fatigue)
  • Nausea
  • Belly, joint, or muscle pain
  • Pneumonia
  • Rash
  • Low red and white blood cell counts

Idelalisib

Idelalisib can cause these common side effects:

  • Diarrhea
  • Pneumonia
  • Fever
  • Fatigue
  • Nausea
  • Cough
  • Belly Pain
  • Chills
  • Rash
  • Low red blood cell, white blood cell, and platelet counts

Ways to manage side effects

To help manage the side effects of these medicines, you may want to:

  • Eat smaller meals, more often throughout the day to avoid tummy trouble.
  • Avoid foods that may irritate your stomach, such as fried foods, high-fiber items, coffee, spicy dishes, dairy products, and raw veggies and fruits.
  • Stay hydrated. Drink 8-12 cups of liquids each day.
  • Stay active. Regular exercise can help you manage your fatigue.
  • Try relaxation techniques, like yoga or deep breathing, to relieve stress.
  • Get enough sleep each night. Try to go to bed and wake up at the same time each day.

Who Should Not Take PI3K Inhibitors?

Doctors don’t know if it’s safe or effective for children younger than 18 years old to take these medicines.

Before you start on idelalisib or duvelisib, let your doctor know if you have or have had:

  • An infection, including cytomegalovirus (CMV, a herpes virus)
  • Colitis or another condition that affects your stomach or intestines
  • A lung disease or breathing problems

You shouldn’t take idelalisib if you’ve had a serious allergic reaction to the medicine or have had a severe skin reaction to any other drug. You should also let your doctor know if you’ve had any liver problems in the past before you start on this drug.

Because of the risk of death, patients should not use duvelisib as a first- or second-line treatment for CLL. 

Idelalisib should not be the first treatment you try for CLL.

Tell your doctor about all the other medicines you take while you use a PI3K inhibitor. These medicines may interact with other treatments. 

How Much Do PI3K Inhibitors Cost?

These medicines can be pricey. Some drug information websites estimate that if you pay cash, the price of duvelisib is around $25,303 for a supply of 56, 15 milligram (mg) oral capsules. The list price for idelalisib is thought to be around $14,550 for a supply of 60, 100 mg tablets.

The companies that make these medicines may provide financial support. You might want to look into these special discounts: 

  • The manufacturer of idelalisib offers a program to help patients cover the cost of the drug. To see if you qualify, you can visit their website.
  • The maker of duvelisib provides a copay program that gives insured patients a discount on their treatment. You can learn more on their site.

Additionally, some nonprofit groups provide help with drug costs. Here are some to check out:

Clinical Trials of PI3K Inhibitors for CLL

Clinical trials are studies that allow researchers to examine the safety and effectiveness of new treatments. These trials may give you the chance to receive a new therapy that isn’t yet available to the public. 

If you’d like to join a clinical trial, you might want to talk to your doctor about which study would be a good fit for you. Additionally, you can search websites and databases, like:

What to Know if You’re a Caregiver

Caring for someone with CLL can be stressful. If they take a PI3K inhibitor, you might worry about the medicine’s possible life-threatening side effects.  

Here are some tips for how to help your loved one:

  • Record any side effects, and report them to the patient’s doctor.
  • Help your loved one stay on their medication schedule.
  • Provide a ride to and from doctor’s appointments. 
  • Take notes at doctor’s appointments, so you can review them later.
  • Help your loved one with chores, but also let them do what they can to stay independent. 
  • Get enough rest, and take care of yourself.

Are Targeted PI3K Inhibitors for CLL Right for Me?

Your doctor can help you determine if you’re a good candidate for a PI3K inhibitor. Here are some factors they may consider:

syringe 3 infographic

Your past treatments. PI3K inhibitors shouldn’t be a first-line treatment. You should try other cancer medicines before you take these drugs.

symptoms 1 graphic

Your overall health. These medicines can be harsh. Your doctor may not want you to take them if you’re in very poor health.

stethoscope calendar graphic

Your medical history. You should tell your doctor if you have certain conditions, like severe liver disease, an infection, lung disease, or colitis, before you use a  PI3K inhibitor.

symptoms 2 graphic

Side effects. These drugs can cause severe or life-threatening side effects. You will need to weigh the risks and benefits of this treatment.

money graphic

Cost.  PI3K inhibitors are expensive. If you can’t get financial help, you may want to reconsider this treatment.

Show Sources

SOURCES:

Leukaemia Foundation: “Chronic lymphocytic leukaemia (CLL).”

MedlinePlus: “Duvelisib,” “Idelalisib.”

Medscape: “Chronic Lymphocytic Leukemia (CLL) Treatment & Management.”

Cell Reports: “miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling.”

American Cancer Society: “Targeted Therapy Drugs for Chronic Lymphocytic Leukemia.”

Secura Bio: “Copiktra.”

Gilead: “Zydelig.”

Leukemia & Lymphoma Society: “Clinical Trials,” “Caregiver Support.”