Immunotherapy itself is not typically a painful procedure. Most treatments are delivered through an IV infusion or an injection under the skin, which feels similar to a routine blood draw or vaccination. The real question for most people is what happens afterward, because immunotherapy can trigger pain-related side effects that range from mild joint aches to more significant inflammation in various parts of the body. These side effects differ substantially from the nausea and nerve damage associated with chemotherapy, and most are manageable when caught early.
What the Infusion or Injection Feels Like
If you’re receiving IV immunotherapy, you’ll feel the needle stick when the IV line goes in. After that, the infusion itself is painless. Sessions typically last 30 to 60 minutes, though some take longer depending on the drug. You sit in a chair, and many patients read, watch something, or nap during the process.
Subcutaneous immunotherapy (injected just under the skin) can cause brief stinging or burning at the injection site. Injection-site pain is one of the most commonly reported complaints with subcutaneous biologics, though how much it bothers people varies widely. In clinical trials, the percentage of patients reporting injection-site pain ranged from under 2% to over 60% depending on the specific drug, the condition being treated, and how pain was measured. For most people, this discomfort is mild and fades within minutes to hours.
Joint and Muscle Pain
Joint pain is the most common pain-related side effect of checkpoint inhibitor immunotherapy, the class of drugs most widely used in cancer treatment today. Estimates of how often it occurs range from 1% to 43% of patients depending on the study, though the 5% to 10% range is a reasonable general estimate. One study of 195 patients receiving a common checkpoint inhibitor found joint pain in about 13% of them, with roughly 5% developing actual inflammatory arthritis.
Muscle pain is the second most common musculoskeletal complaint, reported in 2% to 21% of patients across clinical trials. Both joint and muscle pain are typically graded as moderate on the severity scale used in oncology, meaning they can interfere with daily activities but aren’t usually dangerous. Many patients who’ve already been through chemotherapy describe these side effects as easier to handle than what they experienced before.
For mild joint pain, over-the-counter anti-inflammatory medications are usually enough. When pain is moderate and limiting daily activities, doctors often prescribe a short course of steroids. Patients with more severe joint inflammation may need higher steroid doses and a referral to a rheumatologist. In cases where steroids can’t be tapered without symptoms returning, longer-term medications that calm the immune response can be added without reducing the cancer-fighting benefit of the immunotherapy.
Gut Pain From Inflammation
Immunotherapy works by releasing the brakes on your immune system so it can attack cancer cells. Sometimes the immune system overshoots and attacks healthy tissue too. When it targets the lining of the colon, the result is colitis, which causes abdominal pain, diarrhea, and occasionally bloody stools. Gastrointestinal side effects tend to appear about 6 to 7 weeks after starting treatment, making them one of the earlier internal complications to show up.
The abdominal pain from immunotherapy-related colitis can range from mild cramping to severe discomfort. Catching it early matters because mild colitis is much easier to treat than advanced inflammation. If you develop persistent diarrhea or stomach pain during immunotherapy, your care team needs to know right away.
Skin Reactions
Skin problems are often the very first side effect to appear, sometimes within 2 to 6 weeks of the first dose. Rashes, itching, and painful skin reactions are common across multiple types of immunotherapy. Some patients develop redness and irritation that feels like a sunburn, while others get raised, itchy patches. The severity varies, but most skin reactions are manageable with topical treatments and don’t require stopping immunotherapy.
Nerve Pain
Peripheral neuropathy, the tingling, burning, or numbness that many people associate with chemotherapy, can also occur with immunotherapy, though it’s less common. Neurological side effects from checkpoint inhibitors were initially reported in about 1% of patients, but more recent data puts the number at 1% to 6% for single-drug therapy and up to 14% for combination regimens. Peripheral neuropathy accounts for nearly half of all neurological immune-related events in some studies.
While rare, nerve complications deserve attention. They accounted for roughly 11% of fatal adverse events linked to checkpoint inhibitors in one large analysis. The numbness or tingling usually starts in the hands or feet and can progress if not addressed. This is one area where immunotherapy and chemotherapy side effects overlap, though immunotherapy carries a lower overall risk of neurological events than traditional chemotherapy.
When Side Effects Appear
Most immune-related side effects develop within the first 15 weeks of treatment, but the timeline is unpredictable. Skin reactions tend to come first, followed by gut problems around 6 to 7 weeks. Kidney-related complications, when they occur, tend to appear later, around 15 weeks. In rare cases, side effects have appeared months or even years after completing treatment, with some instances documented up to three years after the first dose.
This delayed timeline is one of the key differences from chemotherapy, where side effects like nausea and hair loss follow a more predictable pattern tied to each treatment cycle. With immunotherapy, the immune system has been fundamentally reprogrammed, and inflammation can develop on its own schedule.
How Pain Compares to Chemotherapy
The nature of pain is different between the two treatments. Chemotherapy pain tends to be tied to direct tissue damage: nerve endings in the hands and feet are harmed by the drugs, the gut lining is damaged, and mouth sores develop from rapidly dividing cells being killed off. Immunotherapy pain, by contrast, comes from inflammation. Your immune system is overreacting, and that inflammatory response causes soreness in joints, cramping in the gut, or burning in the skin.
This distinction matters because inflammation-driven pain generally responds well to anti-inflammatory medications and steroids. Many patients find immunotherapy side effects more tolerable overall than chemotherapy, particularly because immunotherapy doesn’t cause the widespread nausea, hair loss, and bone marrow suppression that define chemotherapy’s side effect profile. That said, severe immune reactions can be serious and occasionally require stopping treatment, so any new or worsening pain during immunotherapy is worth reporting to your care team promptly.