Opdivo (nivolumab) works by removing a “brake” that cancer cells put on your immune system. Normally, your T cells (the immune cells responsible for finding and killing threats) can recognize and attack cancer. But many tumors have found a workaround: they display a protein on their surface that essentially tells T cells to stand down. Opdivo blocks that signal, freeing your immune system to fight the cancer again.
The Immune Checkpoint Opdivo Blocks
Your T cells have a receptor called PD-1 on their surface. Think of it as an “off switch.” When PD-1 connects with certain proteins (called PD-L1 and PD-L2) on other cells, it tells the T cell to stop attacking. This is a normal safety mechanism that prevents your immune system from damaging healthy tissue.
Cancer cells exploit this system. Many tumors produce PD-L1 or PD-L2 on their surface, effectively disguising themselves as healthy tissue. When a T cell approaches and its PD-1 receptor locks onto one of these proteins, the T cell shuts down instead of attacking. The tumor grows unchecked.
Opdivo is an antibody that binds directly to PD-1 on T cells with high affinity, physically blocking PD-L1 and PD-L2 from connecting. With that “off switch” covered, T cells reactivate. They can recognize tumor cells as threats again, multiply in response to cancer-specific signals, and mount an attack. Opdivo also stimulates memory T cells, which may help the immune system remember and respond to the cancer long after treatment ends.
Cancers Opdivo Is Approved to Treat
Opdivo has one of the broadest approval lists of any immunotherapy drug. It is FDA-approved for more than a dozen cancer types, either alone or in combination with other treatments:
- Melanoma (advanced or after surgical removal)
- Non-small cell lung cancer (before surgery or for metastatic disease)
- Kidney cancer (advanced renal cell carcinoma)
- Classical Hodgkin lymphoma (after other treatments have failed)
- Head and neck squamous cell carcinoma
- Bladder and urinary tract cancer (urothelial carcinoma)
- Colorectal cancer (specific subtypes with DNA repair defects, called MSI-H or dMMR)
- Liver cancer (hepatocellular carcinoma)
- Esophageal cancer
- Stomach and gastroesophageal junction cancer
- Malignant pleural mesothelioma
One important detail: unlike some immunotherapies, Opdivo does not require a minimum PD-L1 expression level for most of its approved uses. Patients whose tumors test negative for PD-L1 can still benefit. Clinical trials have consistently shown survival and response improvements even in patients with low or no detectable PD-L1 expression, so testing is used to inform treatment decisions rather than as a strict eligibility requirement.
How Opdivo Is Given
The standard intravenous infusion takes about 30 minutes. For most adults, the dose is either 240 mg every two weeks or 480 mg every four weeks, depending on the treatment plan. When Opdivo is combined with chemotherapy or another immunotherapy drug, the schedule often shifts to 360 mg every three weeks.
In December 2024, the FDA approved a subcutaneous (under-the-skin) injection version called Opdivo Qvantig. This formulation is approved across all adult solid tumor indications and can be given every two, three, or four weeks depending on the cancer type. It offers a faster, potentially more convenient alternative to sitting through an IV infusion.
Why Opdivo Is Often Combined With Yervoy
Opdivo is frequently paired with ipilimumab (Yervoy), another immunotherapy drug that works on a different immune checkpoint called CTLA-4. While Opdivo releases the brake at the PD-1 checkpoint, Yervoy releases a separate brake earlier in the T cell activation process. Blocking both pathways at once can produce a stronger, more durable immune response than either drug alone.
The clinical results of this combination can be striking. In a trial of patients with a specific type of metastatic colorectal cancer (MSI-H or dMMR), those receiving the Opdivo-Yervoy combination had a median time before their cancer progressed of about 54 months, compared to roughly 6 months with standard chemotherapy. That benefit held for patients with liver metastases, a group that typically responds poorly to treatment.
About 30% to 40% of patients don’t respond to a single-agent PD-1 inhibitor and see their disease progress within the first two to three months. The dual-checkpoint approach aims to reach some of those patients. However, the tradeoff is a higher rate of side effects, which is an important consideration when choosing a treatment plan.
Long-Term Survival Results
Immunotherapy’s most notable feature is the possibility of durable, long-lasting responses. In metastatic non-small cell lung cancer, the five-year survival rate for patients treated with the Opdivo-Yervoy combination was 24% when tumors expressed PD-L1, compared to 14% with chemotherapy alone. Even for patients whose tumors had low or no PD-L1 expression, the five-year survival rate was 19% versus 7% with chemotherapy.
Perhaps the most encouraging finding: among patients who survived five years, roughly two-thirds were no longer on any cancer treatment. They had stopped Opdivo and had not started any other therapy. Even patients who had to discontinue treatment early due to side effects fared well, with a five-year survival rate of 39%. This suggests that once the immune system is effectively activated against a cancer, the response can persist long after the drug is out of your body.
Side Effects and Immune-Related Reactions
Because Opdivo works by unleashing the immune system, most of its side effects stem from the immune system attacking healthy tissue along with the cancer. These are called immune-related adverse events, and they can affect nearly any organ.
Skin reactions are the most common, including rash, itching, and sometimes vitiligo (patches of skin losing color). These occur in up to 71% of patients across checkpoint inhibitor therapies. Joint and muscle pain affects up to 40% of patients in clinical trials. Digestive issues like diarrhea occur in up to 19% of patients on Opdivo alone, though rates climb significantly when it’s combined with Yervoy.
More serious but less common reactions include lung inflammation (pneumonitis), which occurs in about 3% of patients on Opdivo alone and up to 10% when combined with Yervoy. Colitis, an inflammation of the colon, ranges from 8% to 27% depending on the regimen. These reactions are manageable when caught early, which is why treatment teams monitor bloodwork and symptoms closely throughout the course of therapy.
What to Expect During Treatment
After starting Opdivo, you won’t feel the drug working in any obvious way. The immune response builds gradually, and doctors typically order the first imaging scans (CT or PET) around six to nine weeks into treatment, usually after three or four infusion cycles. This gives the immune system enough time to mount a measurable response.
One phenomenon specific to immunotherapy is “pseudoprogression,” where tumors may initially appear larger on scans because immune cells are flooding into the tumor site. This can look like the cancer is growing when it’s actually being attacked. Your oncology team will take this into account when reading early scans and may recommend continued treatment with follow-up imaging to confirm whether the tumor is truly progressing or responding.
Treatment continues on its regular schedule until the cancer progresses, side effects become unmanageable, or a planned course is completed. Some patients remain on Opdivo for a year or two; others stop sooner. As the long-term survival data shows, stopping treatment doesn’t necessarily mean the benefit stops. For a meaningful portion of patients, the immune system continues to control the cancer on its own.