Recognizing Side Effects in Novel Treatments for CLL Can Be Crucial

The landscape of cancer care has been changing with the increased use of novel therapies. Targeted therapies and immunotherapies can be used as single agents or in combination with other therapies to treat a variety of cancers, including chronic lymphocytic leukemia (CLL), the most common leukemia in adults in the United States. Recently approved novel therapies for CLL include the immunotherapies Arzerra (ofatumumab) and Gazyva (obinutuzumab) and targeted agents Imbruvica (ibrutinib) and Zydelig (idelalisib). These therapies extend remission times and can also improve survival.

Each of these agents has unique side effects, presenting challenges for patients and caregivers. Knowing how to recognize and manage these side effects can help patients safely continue their treatments and maximize their full therapeutic benefit. While some of the more common or serious side effects are discussed here, this list is not all-inclusive, and patients should discuss all potential side effects with their oncology teams.

Arzerra and Gazyva are monoclonal antibodies that target CD20, a protein on B cells that are abnormal in CLL. The most common side effects are reactions occurring during infusion, mainly during the first infusion. Symptoms include shortness of breath, rash, flushing, fever and back pain, although more serious reactions can occur. Patients will receive pre-medications and be monitored by nurses throughout each infusion, but should let the staff know immediately if they have any of these symptoms or feel any different during the infusion, including up to 24 hours afterwards. Arzerra can cause diarrhea, but rarely also intestinal obstruction; therefore, any gastrointestinal pain or changes in bowel movements should be reported to the oncology team.

Very serious, but less common, reactions to monoclonal antibodies include hepatitis B reactivation and progressive multifocal leukoencephalopathy, a rare, life-threatening viral disease that damages the brain’s white matter, so any changes in thought process or confusion should be reported. It is recommended that patients do not receive any live vaccinations while receiving either of these medications, since these patients are immunocompromised and face a risk of developing the condition they are being vaccinated against.

Imbruvica blocks an enzyme along a cell-signaling pathway that plays a role in abnormal cell growth in CLL. It is taken by mouth once daily, at the same time each day. The most common side effects are low blood counts, diarrhea, nausea, muscle pain, infections and fatigue. A serious but rare side effect is atrial fibrillation, an irregular heartbeat. A patient should contact his medical team immediately if he has any heart palpitations, chest pain or dizziness. Zydelig, taken by mouth twice daily, targets receptors on the CLL cell that are involved in cell function and development. Low blood counts, diarrhea, nausea and fatigue are some of the more common reactions. Serious side effects include severe diarrhea (more than seven stools per day) with colitis, liver inflammation or damage, severe skin reactions and inflammation of the lungs.

It is important to know that both Imbruvica and Zydelig can initially cause an increase in lymphocytes in the blood, and it may take several months for the lymphocytes to decrease. This is not disease progression or a poor response, but rather a release of the lymphocytes from the lymph nodes as the medications affect the CLL cells. All four of these agents can cause low blood counts, so any fever, bleeding, bruising, shortness of breath or change in mental status should be reported immediately. Imbruvica can interfere with platelet function; therefore, any unexplained bleeding or bruising should be reported, even if the patient has a normal platelet count.

Taking medications as prescribed is important in order to obtain full benefit from the therapy. It’s also important to avoid drugs that can interact with Imbruvica or Zydelig, potentially increasing side effects or decreasing the effectiveness of the medications. Patients should notify their oncology teams if they start any new medications, including over-the-counter medicines. Grapefruits or Seville oranges (used in marmalades) can increase the amount of Imbruvica or Zydelig in the blood, leading to increased side effects, and also should be avoided.

These newer therapies for CLL have many therapeutic benefits, and can improve quality of life for patients. Understanding the potential side effects and knowing what to expect can help patients receive their treatments safely, and hopefully can decrease anxiety for them and their families. Oncology teams can provide printed materials with medication information and direct patients and caregivers to appropriate online resources for additional information. Pharmaceutical companies have websites designed to provide patients and families with drug education.

Patients often fear that having side effects may mean they’ll have to discontinue a therapy that is working, so they are reluctant to share these effects with their medical teams. However, most of the side effects of these newer agents can be managed simply by adjusting the dose or schedule, or by adding supportive medications. Honestly reporting reactions is recommended because it can lead to improvements in comfort and safety. Medication effects are different for each patient, and medical teams can typically provide relief by minimizing the side effects while keeping patients on therapy, which maximizes the benefits of these drugs.

Moreover, many common side effects can be managed at home with supportive care. For example, mild diarrhea can be controlled by adding bulk to the diet, increasing fluids to prevent dehydration and performing good rectal care to prevent discomfort. Hand washing and avoiding people with respiratory symptoms can decrease the risk of infection when blood counts are low, and avoiding sharp instruments or activities involving hard physical contact can reduce the risk of bleeding. Rashes are usually mild, and can be relieved with topical creams and warm showers. Eating a balanced diet, drinking enough fluids and walking daily can help with fatigue while maintaining strength and muscle tone. Hugging family members is always encouraged, and having healthy visitors can lift spirits and provide distraction.