Is Fatigue After Immunotherapy Infusion Normal?
Yes, fatigue after immunotherapy infusion is a common and expected side effect that occurs in a significant proportion of patients receiving immune checkpoint inhibitors. 1
Incidence and Severity
Fatigue is one of the most frequently reported adverse events with immunotherapy:
Cancer-related fatigue from immunotherapy occurs in 12% to 37% of patients receiving monotherapy, and can increase to 71% when immunotherapy is combined with chemotherapy, monoclonal antibodies, or other targeted therapies. 1
In clinical trials of nivolumab (Opdivo), fatigue was reported in 36% of patients receiving the drug, with severe (Grade 3-4) fatigue occurring in only 0.4% of cases. 2
With pembrolizumab (Keytruda), fatigue is listed as one of the common side effects that patients should be informed about prior to treatment. 3
The NCCN guidelines recognize fatigue as a common symptom that may indicate various immune-related adverse events, including thyroid disorders, hypophysitis, or adrenal insufficiency when accompanied by other symptoms. 1
Clinical Characteristics
The fatigue associated with immunotherapy has distinct features:
It differs from normal tiredness by its severity, persistence, and inability to be relieved through rest or sleep. 1
The fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness that is not proportional to recent physical activity and interferes with usual functioning. 1
Fatigue may occur alone or be accompanied by other symptoms such as headache, nausea, or musculoskeletal pain, which are also common with immunotherapy. 1, 2
When to Be Concerned
While fatigue is expected, certain presentations warrant closer evaluation:
Fatigue accompanied by weight changes, nausea, chest pain, shortness of breath, or arrhythmias may indicate serious immune-related adverse events such as thyroid disorders, hypophysitis, adrenal insufficiency, or myocarditis. 1
The ESMO guidelines recommend that healthcare professionals should acknowledge the reality and impact of fatigue, provide information about its possible causes and course, and conduct careful assessment on a regular basis. 1
Shared decision-making between patients and healthcare providers should occur during all phases of care regarding fatigue management. 1
Management Approach
For routine post-infusion fatigue:
Most cases of mild to moderate fatigue (Grade 1-2) can be managed with symptomatic support and do not require modification of immunotherapy dosing. 1, 4
Patients should be informed that fatigue is an expected side effect and provided with information about management strategies available. 1
Regular monitoring throughout treatment is essential to distinguish between expected fatigue and fatigue that signals a more serious immune-related adverse event requiring intervention. 1
Important Caveat
If fatigue is accompanied by endocrinological symptoms (such as persistent headache, vision changes, extreme thirst, or significant weight changes), cardiovascular symptoms (chest pain, palpitations), or respiratory symptoms (dyspnea), immediate evaluation is necessary as immunotherapy can cause fatigue secondary to endocrine disorders, myocarditis, or other serious immune-related adverse events. 1