Side effects of ibrutinib and idelalisib treatment

In this review, the authors look at the most common adverse events related to ibrutinib and idelalisib, B-cell inhibitors. The study concluded that both ibrutinib and idelalisib are effective at treating B-cell cancers, and the side effects are within a normal range compared to other similar treatments.

Ibrutinib and idelalisib are biological treatments for B-cell cancers. They work by stopping the pathways that B-cells use to reproduce. The diseases these drugs are used for include chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). These drugs are used to treat relapsed or refractory (difficult to treat) cancers. Previous studies have shown these medications have good long-term outcomes and high response rates.

However, these medications also have side effects (adverse events; AEs). A comprehensive review of the side effects of these medications is needed.

This study reviewed the most common AEs of ibrutinib and idelalisib that have been reported during clinical trials.

Ibrutinib: Ibrutinib (IB) is given in larger doses (560mg) to patients with MCL than patients with CLL (420mg). It is also often given in combination with rituximab. Higher doses may be related to a lower ability to tolerate the drug. However, these studies were small.

Minor bruising is common when taking IB. IB should not be stopped or interrupted unless a major bleeding event occurs.

IB may increase the risk of having an abnormal heart rhythm, such as atrial fibrillation (AFib). However, if AFib develops IB should not be stopped. There is no evidence that stopping IB will cure AFib, and stopping the IB treatment would make the patient’s long term outcomes worse.

Blood pressure should be measured regularly when taking IB. IB should not be stopped if high blood pressure develops.

Diarrhea, a rash, and brittle hair and nails are common when taking IB. Diarrhea may be treated with medication. Rashes usually get better on their own. IB should not be stopped if these conditions develop.

Between 11% and 51% of patients stop taking ibrutinib because of AEs. Fatal AEs have been reported in 1% to 9% of patients.

Idelalisib: Idelalisib (ID) is given in smaller doses (150mg) twice a day. ID is often given in combination with rituximab for patients with CLL. It is often given alone for patients with FL. Taking rifampicin (a common antibiotic) or similar medications may reduce the effectiveness of ID.

Diarrhea is common when taking ID. It is more common in patients who have not yet had any treatment for their cancer. Usually the diarrhea is less severe if it occurs early in treatment. If it occurs later in treatment (7 months on average), it is usually more severe. ID may need to be interrupted if the diarrhea is severe and lasts more than 1 or 2 days. After ID is stopped, the diarrhea gets better in 1 week to 1 month.

Pneumonia is also common when taking ID. Approximately 20% of patients will get pneumonia. A non-infectious inflammation of the lungs, known as pneumonitis, is also common (3%). Both pneumonia and pneumonitis have had fatal events. ID should not be stopped for bacterial pneumonia. ID should be stopped for non-infectious pneumonitis.

Liver problems, known as hepatotoxicity, may occur. Approximately 50% of patients experienced an increase in liver enzymes when taking ID. This usually occurs within the first 3 months of treatment. ID does not need to be discontinued if the liver enzymes are within 5 times the normal range. ID should be paused if they increase to between 5x and 20x the normal range. ID should be discontinued permanently if they increase above 20x the normal levels.

Changes in blood count and rashes are also common. Blood counts should be monitored, but ID usually does not need to be stopped. If a very serious rash occurs, ID should be stopped.

Between 9% and 20% of patients stop taking ID because of AEs. One trial noted a higher discontinuation rate (45%) when taken in combination with rituximab. Fatal AEs have been reported in 3% to 8% of patients.

The authors concluded that both ibrutinib and idelalisib are effective at treating B-cell cancers, and the side effects are reasonable compared to other similar treatments.