Immunotherapy can cause weight loss, and it happens more often than many patients expect. In a study of 370 patients with advanced lung cancer receiving immunotherapy combined with chemotherapy, 38% lost more than 5% of their body weight during treatment. Weight loss during immunotherapy stems from several overlapping causes, some related to the drugs’ side effects and others tied to the underlying cancer itself.
How Immunotherapy Triggers Weight Loss
Immune checkpoint inhibitors work by releasing the brakes on your immune system so it can attack cancer cells. But that unleashed immune response doesn’t always stay focused on the tumor. It can turn against healthy tissues throughout your body, creating a chain of side effects that reduce appetite, impair nutrient absorption, or speed up your metabolism.
The most direct path to weight loss is through the gut. Immunotherapy can cause inflammation in the colon and small intestine, leading to diarrhea that ranges from mild to severe. In some cases, the small intestine develops damage resembling celiac disease, where the tiny finger-like projections that absorb nutrients (called villi) flatten out. When that happens, your body struggles to extract calories and nutrients from food even when you’re eating normally. More severe cases involve deep ulceration of the intestinal lining, compounding the problem. Persistent diarrhea alone can drive significant fluid and calorie losses over weeks of treatment.
Nausea and reduced appetite are also common. Even without overt gut inflammation, many patients simply feel less hungry during treatment. When eating becomes uncomfortable or unappealing, calorie intake drops gradually, and weight follows.
Thyroid Problems and Metabolism Changes
Immunotherapy frequently disrupts thyroid function, and thyroid hormones are a major regulator of your metabolism. Between 1% and 35% of patients develop some form of thyroid dysfunction during treatment, depending on the specific drug and how it’s measured.
The pattern often unfolds in two phases. First, the immune system attacks the thyroid gland, causing it to release a burst of stored hormone into the bloodstream. This creates a temporary hyperthyroid state where your metabolism runs too fast. You might notice a racing heart, sweating, anxiety, and weight loss during this window. In one study of 48 patients on pembrolizumab, 10 developed thyroid problems, and six of them went through this early hyperthyroid phase before their thyroid burned out.
After that initial surge, the damaged thyroid can no longer produce enough hormone, and you swing into hypothyroidism. At that point the metabolic picture reverses: fatigue, constipation, cold sensitivity, and often weight gain. So immunotherapy-related thyroid disease can cause weight loss early on, then potentially weight gain later, sometimes in the same patient over the course of a few months. Most people who develop hypothyroidism from immunotherapy end up on thyroid hormone replacement for the long term.
Cancer Cachexia vs. Treatment Side Effects
Not all weight loss during immunotherapy comes from the drugs. Cancer itself, particularly advanced cancer, can trigger a wasting syndrome called cachexia. This is a distinct biological process where the tumor drives continuous loss of muscle mass, sometimes with fat loss as well. Cachexia is defined as losing more than 5% of body weight over six months, or losing more than 2% in someone who already has a low body mass index.
The critical difference is that cachexia doesn’t respond to simply eating more. Regular nutritional support won’t reverse it because the wasting is driven by inflammatory signals from the tumor and the body’s response to it. Treatment side effects like diarrhea or nausea, on the other hand, are potentially manageable. If the gut inflammation is treated or the nausea is controlled, appetite and absorption can improve.
Distinguishing between the two matters because it changes the approach. Doctors sometimes use CT scans to measure muscle mass around the spine, tracking whether muscle tissue is shrinking independent of overall weight. This is important because weight alone can be misleading. Steroids and fluid retention can mask muscle loss, making someone appear stable on the scale while their body composition deteriorates underneath.
Why Some Patients Gain Weight Instead
Weight gain during immunotherapy is also real, and it often catches patients off guard when they’ve been told to watch for weight loss. Two main factors drive it.
The first is hypothyroidism. Once the thyroid is damaged and hormone levels drop, metabolism slows. Patients feel fatigued, move less, and their bodies burn fewer calories at rest. Without thyroid replacement medication (or before the dose is optimized), weight creeps up.
The second, and possibly more common, cause is steroid use. About one-third of patients on checkpoint inhibitors end up taking corticosteroids at some point during treatment, usually to manage immune-related side effects like colitis, skin reactions, or brain swelling from metastases. Steroids increase appetite, promote fat storage (especially around the face and midsection), and can cause fluid retention. Prolonged steroid use creates a pattern sometimes called iatrogenic Cushing’s syndrome, with weight gain, depression, fatigue, elevated blood sugar, and eventually the risk of adrenal insufficiency when the steroids are tapered.
Weight Loss and Treatment Outcomes
Losing a significant amount of weight during immunotherapy is not just uncomfortable. It may signal worse outcomes. In the lung cancer study mentioned earlier, nearly 40% of patients who were actually responding to treatment (meaning their tumors were shrinking) still lost more than 5% of their body weight. That finding is important because it shows weight loss isn’t simply a marker of treatment failure. Even when immunotherapy is working against the cancer, the body can still lose ground nutritionally.
Cachexia in particular is associated with immune dysfunction, which creates a troubling cycle: the wasting syndrome weakens the very immune system that checkpoint inhibitors are trying to activate. Patients with significant muscle loss before starting immunotherapy tend to have poorer outcomes, suggesting that nutritional status at baseline plays a role in how well the treatment works.
Managing Weight During Treatment
Clinical guidelines on nutrition during immunotherapy are still limited. The American Society of Clinical Oncology has acknowledged that evidence for specific dietary and weight loss interventions during cancer treatment remains thin. What is recommended is regular physical activity, including both aerobic exercise and resistance training, during treatment with curative intent. Resistance exercise in particular helps preserve muscle mass, which is the tissue most at risk during both cachexia and treatment-related weight loss.
From a practical standpoint, tracking your weight weekly gives you and your care team early warning of changes in either direction. Small, frequent meals may be easier to tolerate than large ones if nausea or early fullness is a problem. If you develop persistent diarrhea (more than a few loose stools per day), that warrants prompt attention because it could indicate colitis that needs specific treatment rather than just dietary adjustment.
Thyroid function is typically monitored with blood tests before each treatment cycle, so thyroid-related weight changes are usually caught and managed with medication. The trickier scenario is gradual weight loss from reduced intake that builds slowly over months, often dismissed as expected during cancer treatment. Keeping a rough food diary or simply noting when your clothes fit differently can help you flag changes before they become severe.