Yes, fatigue is one of the most common side effects of immunotherapy and is frequently reported as the most prevalent adverse event across multiple immunotherapy drug classes. Fatigue can range from mild tiredness to severe physical and mental exhaustion that interferes with work, exercise, and daily activities. It is particularly common in patients receiving immune checkpoint inhibitors. While immunotherapy-related fatigue often improves after treatment ends, some patients continue to experience symptoms for weeks or even months during recovery. 

How Common Is Fatigue With Immunotherapy?

疲劳 is one of the most commonly reported side effects of immunotherapy and occurs in a significant proportion of patients receiving these treatments. It is particularly common among patients treated with immune checkpoint inhibitors, including PD-1, PD-L1, and CTLA-4 inhibitors.

Clinical studies have reported fatigue in approximately 16% to 37% of patients receiving single-agent PD-1 inhibitors, although the incidence can vary depending on the specific drug, cancer type, and study population. Rates of fatigue are generally higher with combination immunotherapy regimens, such as those that combine PD-1 and CTLA-4 inhibitors.

Fatigue is also reported with other forms of immunotherapy, including cytokine therapies such as interleukin-2 (IL-2) and interferon. These treatments are associated with more pronounced systemic immune activation and may produce higher rates and greater severity of fatigue, along with other flu-like symptoms.

What Causes Fatigue During Immunotherapy?

Immunotherapy-related fatigue is a complex side effect with multiple contributing factors rather than a single underlying cause. The mechanisms can vary from person to person and may involve both the treatment itself and the body’s response to it.

• Immune System Activation
  Immunotherapy works by stimulating the immune system to recognize and attack cancer cells. This heightened immune activity requires substantial energy, and the body may expend significant resources maintaining ongoing immune surveillance and response, contributing to feelings of fatigue.
• Inflammation and Cytokine Release
  As the immune system becomes activated, it releases signaling proteins called cytokines. These inflammatory molecules can directly trigger fatigue, producing symptoms similar to those experienced during a viral illness, such as exhaustion, low energy, and reduced stamina.
• Endocrine (Hormonal) Disruption
  Some immune checkpoint inhibitors can cause immune-related effects on hormone-producing glands. Conditions such as hypothyroidism, adrenal insufficiency, and inflammation of the pituitary gland (hypophysitis) can develop during treatment and may lead to significant fatigue that is independent of the cancer itself. Because these conditions are often treatable, appropriate evaluation is important when fatigue becomes persistent or severe.
• 贫血
  In some cases, immunotherapy-related immune effects can interfere with red blood cell production or survival. Reduced red blood cell levels (anemia) can decrease oxygen delivery throughout the body, contributing to tiredness, weakness, and decreased physical endurance.
• Sleep Disruption and Other Treatment Effects
  Pain, anxiety, stress, and other treatment-related side effects may interfere with normal sleep patterns. Poor sleep quality can worsen daytime fatigue and may compound the effects of immune activation and inflammation.

How Does Immunotherapy Fatigue Compare to Chemotherapy Fatigue?

Fatigue can occur with both chemotherapy and immunotherapy, but the pattern and underlying causes may differ.

Chemotherapy-related fatigue is often more acute and closely tied to treatment cycles. Many patients feel their worst in the days immediately after an infusion, followed by some improvement before the next cycle begins.

Immunotherapy-related fatigue, by contrast, may be more chronic and unpredictable. It can develop at any point during treatment and may not follow a clear pattern based on dosing or infusion timing.

Another important difference is that immunotherapy can sometimes cause endocrine side effects, such as hypothyroidism. If hypothyroidism is not recognized and treated, fatigue may persist long after immunotherapy has ended. However, once identified, hypothyroidism is typically treatable with thyroid hormone replacement.

For patients whose fatigue is driven by endocrine dysfunction, addressing the underlying hormonal imbalance can often lead to significant improvement in energy levels.

进一步阅读： Managing Immunotherapy Side Effects — Memorial Sloan Kettering Cancer Center

How Long Does Immunotherapy Fatigue Last?

The duration of immunotherapy-related fatigue varies from person to person and depends on the underlying cause. While many patients experience gradual improvement after treatment ends, some may continue to experience fatigue for weeks or months.

Acute fatigue related to immune activation and cytokine release often improves within days to a few weeks after treatment. As inflammation subsides, energy levels may gradually return to baseline.

However, fatigue caused by endocrine 副作用 can last longer. Immunotherapy may trigger conditions such as hypothyroidism or adrenal insufficiency, and fatigue associated with these hormonal imbalances may persist until the underlying condition is identified and appropriately treated.

Some patients also report lingering fatigue for months after completing immunotherapy. This may be part of a broader condition known as cancer-related fatigue (CRF), which is an ongoing area of research. Cancer-related fatigue can involve physical, behavioral, and neurological factors and may persist even after treatment has ended.

Patients should inform their healthcare team about persistent, severe, or worsening fatigue. In some cases, fatigue may be a sign of an underlying immune-related adverse event that requires medical evaluation and treatment.

Tips for Managing Fatigue During Immunotherapy

Fatigue is a common side effect of immunotherapy, but several practical strategies may help patients maintain energy levels and improve day-to-day functioning during treatment.

• Stay Active With Light Exercise
  While it may seem counterintuitive, gentle physical activity can help reduce fatigue. Short walks, stretching, yoga, or other low-impact exercises for as little as 10–20 minutes per day may help maintain energy, support physical conditioning, and improve mood without overexertion.
• Pace Yourself
  Try to plan activities around times of day when your energy is highest. Prioritize important tasks, break larger activities into smaller steps, and allow time for rest between activities to avoid becoming overly fatigued.
• Rest Strategically
  Short naps can help restore energy, particularly during periods of increased fatigue. Limiting naps to approximately 15–20 minutes may help prevent interference with nighttime sleep.
• Maintain Good Nutrition and Hydration
  Adequate nutrition and fluid intake play an important role in supporting energy levels. Eating balanced meals and staying hydrated may help reduce fatigue. Patients experiencing reduced appetite, weight loss, or difficulty meeting nutritional needs may benefit from consulting a registered dietitian.
• Practice Good Sleep Hygiene
  Pain, anxiety, stress, and treatment-related side effects can interfere with sleep quality. Establishing consistent sleep habits and addressing factors that disrupt sleep may help improve daytime energy. Patients experiencing ongoing insomnia should discuss their symptoms with their oncology team.
• Report Severe or Sudden Fatigue Promptly
  Unusual, severe, or rapidly worsening fatigue should not be ignored, especially when accompanied by other new symptoms. In some cases, significant fatigue may be a sign of an immune-related adverse event (irAE), such as thyroid dysfunction, adrenal insufficiency, or, more rarely, an adrenal crisis. Prompt medical evaluation can help identify and treat these conditions before they become more serious.