What Are the Side Effects of Immunotherapy?

  • The side effects of immunotherapy can be different from those associated with standard treatments.
  • One study found that fatigue was the most common side effect, along with fever, chills, nausea, and reactions at the site of the infusion.

Medically reviewed by Gordon Freeman, PhD

New drugs that stimulate the patient’s immune system to attack tumors have achieved some dramatic and long-lasting benefits in several forms of cancer. A few drugs are already approved for wide use and many more are in the research pipeline. Because these immunotherapy agents work differently than chemotherapy, the side effects of immunotherapy can be different from those associated with standard treatments.

One of cancer cells’ survival strategies is to hide from immune soldier T-cells and exploit natural “checkpoint” proteins that suppress T-cell activity. Some immunotherapy agents disable these checkpoints, removing the brakes so T-cells can mount a stronger immune attack on cancer cells. In this way, the drugs don’t directly assault the cells; instead, they free the patient’s own defensive forces to destroy cancers.

But it’s a two-edged sword. Freed from checkpoint restraint, the surging immune response can overshoot its target and attack healthy tissues and organs, similar to an autoimmune disorder.

“Immunotherapies are pretty well tolerated – there’s no hair loss or blood cell abnormalities. There are not cell poisons. But they have a different set of potential side effects,” says Dana-Farber’s Gordon Freeman, PhD, whose research has been fundamental to the development of immunotherapies that have emerged in the past several years.

Common and serious side effects

One study found that fatigue was the most common side effect, along with:

  • Fever
  • Chills
  • Nausea
  • Reactions at the site of infusion

Immunotherapy drugs such as ipilimumab, which targets the CTLA-4 checkpoint, and PD1/L1 checkpoint blockers like nivolumab and pembrolizumab are approved for melanoma, lung, and kidney cancer. Patients who receive these therapies need to be monitored for potentially more serious adverse effects such as:

  • Pneumonitis (inflammation of the lungs resulting in cough and difficulty breathing)
  • Colitis (inflammation of the large bowel leading to diarrhea)
  • Hepatitis and pancreatitis
  • Skin rashes
  • Endocrine disorders including thyroid abnormalities and adrenal insufficiency

Fortunately, the vast majority of such reactions can be controlled with immune suppressive drugs such as corticosteroids and antihistamines that tamp down the inflammatory overreaction.

Side effects are best treated when diagnosed early. Patients are always asked to report anything that seems unusual to their care team who can determine if it’s related to their immunotherapy treatment.