Side Effect Central is a new series of articles designed to help patients with melanoma and their caregivers understand the side effects that typically accompany melanoma treatments. Our goal is to explain what side effects to expect during treatment and to encourage communication with your medical team about these side effects.

Side effects can range from mild to very serious, and doctors cannot predict who will suffer more side effects than others. Serious side effects can cause patients to interrupt or discontinue treatment, so managing them is a critical piece of melanoma treatment.

What is colitis?

Colitis is an inflammation of the gastrointestinal lining. It is among the most common side effects observed in patients receiving immunotherapy or immune checkpoint inhibitors, especially CTLA-4 inhibitors, such as ipilumimab (Yervoy). In fact, 30-45% of patients receiving CTLA-4 inhibitors will experience some level of colitis. Colitis is cited as a frequent reason for treatment interruption and discontinuation.

Inflammation in the gastrointestinal lining can cause bloating, cramping, diarrhea, and pain in the abdomen. Excessive watery diarrhea is a symptom of colitis (albeit not definitive, due to multiple other causes of diarrhea) that can indicate when a patient might be developing colitis. Moderate watery diarrhea, increasing to more than five loose bowel movements per day, usually arises five to ten weeks after immunotherapy begins, or after the second to third dose of immunotherapy.

What should patients know?

Although colitis can be a serious and potentially life-threatening complication, most patients will not have colitis that develops into a more serious condition requiring immediate intervention. Less than 11% of patients treated with single-agent ipilimumab or combination regimens containing ipilimumab will develop severe colitis. Infrequent but possible complications arising from serious colitis include bowel perforation, dehydration, hospitalization, sepsis, and shock. Patients should promptly communicate with their healthcare team and seek treatment when observing any of the symptoms listed below.

Mild to moderate symptoms—report to your health care team

• Abdominal pain
• An increase of 4-6 stools per day
• Blood or mucus in stool

Serious symptoms—report to your health care team

• An increase of 7 or more stools per day
• Decreased appetite
• Fever
• Rapid change in gastrointestinal function
• Severe cramping and persistent abdominal pain

Call 911

• Shock, distress, abnormal or unstable blood pressure

Why does colitis occur?

Immunotherapy is designed to supercharge the immune system. Unfortunately, the gastrointestinal tract can become susceptible to an immune system-provoked injury as an unintended consequence. Although immunotherapy is created with targeted properties aimed at the tumor’s environment, sometimes it non-specifically activates too much of the immune system throughout the body.

Nearly every organ system in the body is at risk for an unprovoked injury by CTLA-4 inhibitors. However, immunotherapy works so well in many patients that the risk of side effects is deemed worthwhile to achieve the possible results. Prompt and thorough communication about side effects by patients with their medical team allows for appropriate clinical support, and these two together allow immunotherapy to be used safely and successfully in many patients. Individual perspectives about treatment ideals should be discussed with your clinician.

What can a clinician do for colitis?

Rapid identification and treatment can reduce the risk of progression from mild colitis. Management can avoid drug interruption or discontinuation and allow a patient to remain on therapy. Once a definitive diagnosis is made, supportive hydration, along with drugs such as loperamide, diphenoxylate/atropine, or a slow steroid taper may be given. Severe colitis may require intravenous steroids, such as budesonide, infliximab, or vedolizumab.

 

Bottom line: Patients should communicate regularly with their medical team about any of the signs of colitis noted above. Clinicians can then manage and treat the colitis in order to allow patient to remain on immunotherapy or resume treatment as quickly as possible.

 

Where can I find more information on your website?

https://www.aimatmelanoma.org/melanoma-learning-center/side-effect-management-guides/

https://themelanomanurse.org/side-effect-search-section/

https://www.aimatmelanoma.org/wp-content/uploads/AIM-YERVOY-MULTIPAGE.pdf

https://www.aimatmelanoma.org/wp-content/uploads/AIM-OPDIVO-YERVOY-MULTIPAGE-1.pdf

 

References:

Frey C and Etminan M. Adverse Events of PD-1, PD-L1, CTLA-4, and LAG-3 Immune Checkpoint Inhibitors: An Analysis of the FDA Adverse Events Database. Antibodies (Basel). 2024;13(3):59. doi: 10.3390/antib13030059.

Ho C and Samlowski W. Outcome of an Accelerated Treatment Algorithm for Patients Developing Diarrhea as a Complication of Ipilimumab-Based Cancer Immunotherapy in a Community Practice.

Curr Oncol. 2024;31(6):3529-3545. doi: 10.3390/curroncol31060260.

Machado AP, Shaikh AS, Saji A et al. Outcomes of Budesonide as a Treatment Option for Immune Checkpoint