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Immunotherapy Side Effects: Symptoms and Management

Web Exclusives — July 11, 2022

Many side effects of immunotherapy can be effectively managed if they are detected early. Although the symptoms are usually mild and occur early in the treatment process, it is important that patients and caregivers promptly report any symptoms to the care team for appropriate management.

Symptoms to Look For

Immunotherapy is a relatively new category of cancer treatment, and it may cause some immune-related side effects in patients. Most side effects associated with immunotherapy are mild or moderate and can be managed if detected early. Therefore, it is important that patients and their caregivers know what symptoms to look for. These symptoms may include the following side effects1:

  • Digestive: diarrhea, blood or mucus in the stool, severe abdominal pain
  • Endocrine: fatigue, weight loss, nausea, vomiting, thirst or appetite increase, polyuria
  • Skin: extensive rash, severe pruritus
  • Respiratory: shortness of breath, coughing
  • Neurologic: headache, confusion, muscle weakness, numbness
  • Arthralgia or swelling joints
  • Myalgia
  • Unexplained fever
  • Hemorrhagic syndrome
  • Severe loss of vision in one or both eyes

Such side effects can be common (affecting more than 10% of patients), infrequent (about 5%-10%), or rare (less than 5% of patients). The common side effects include dermatitis, pruritus, fevers, chills, fatigue, diarrhea, and colitis. Uncommon side effects include hepatitis or liver enzyme abnormalities, endocrinopathies, and vitiligo.2 The side effects usually occur during the first 12 weeks of treatment, but some may start later and be potentially severe or even life-threatening.3

Clinical trials show that skin-related side effects typically occur early, usually after receiving the second cycle of treatment, whereas hypophysitis and liver side effects usually occur after 8 weeks of treatment. Hepatitis and hypophysitis have been reported up to 1 year after the discontinuation of therapy.4

The side effects related to immunotherapy are more common in organs with extensive environmental interfaces (such as the skin, lungs, liver, and the gastrointestinal tract) or organs harboring presumed pre-existing autoimmunity (such as the thyroid and joints). However, the side effects can occur in essentially any organ system, including the heart, bone marrow, kidneys, bones, and the pituitary gland.5

How to Manage the Side Effects of Immunotherapy

Depending on the severity of symptoms, there are several ways to manage the side effects of immunotherapy with reasonable effectiveness. For example, mild side effects may be managed with supportive care, whereas severe side effects may be treated with steroids or with the suspension or discontinuation of the treatment.2

Examples of supportive care include pain management, nutritional support, counseling, exercise, music therapy, meditation, and palliative care. Supportive care is not meant to treat cancer directly. Its goal is to address the physical, psychosocial, and spiritual needs of patients throughout treatment to improve their quality of life.6

For severe side effects, oncologists may consider the use of steroids and other immunosuppressive drugs, refer the patient to organ specialists, or temporarily suspend the treatment. Immunotherapy may be discontinued in cases of severe immune dysfunction that is life-threatening, severe, and recurring, or if the symptoms are moderate but persist despite appropriate treatment.1

In any case, prompt management is needed as soon as the patient has side effects to avoid any severe or life-threatening complications. However, patients should avoid self-management of the symptoms without coordination with their oncologist or primary care provider. The best action is for the patient to report any complications to his or her care team promptly.

References:

  1. Champiat S, Lambotte O, Barreau E, et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Annals of Oncology. 2016;27:559-574.
  2. Hoffner B, Zitella LJ. Managing side effects of cancer patients treated with immunotherapy. Journal of the Advanced Practitioner in Oncology. 2018;9:287-292.
  3. Scotte F, Ratta R, Beuzeboc P. Side effects of immunotherapy: a constant challenge for oncologists. Current Opinion in Oncology. 2019;31:280-285.
  4. Sanchez K, Page DB, Urba W. Immunotherapy Toxicities. Surgical Oncology Clinics of North America. 2019;28:387-401.
  5. Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nature Reviews Clinical Oncology. 2022;19:254-267.
  6. Lammersfeld C. Cancer supportive care improves quality of life and symptom management. www.cancercenter.com/community/blog/2020/12/cancer-supportive-care.

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