Ipilimumab Therapy - Yervoy
Four doses of ipilimumab alongside nivolumab gave melanoma patients a median survival of six years, and put half of them through a serious side effect. Both facts belong in the same sentence. This guide explains where the drug acts, which cancers it treats, how the bowel and hormone glands are watched, and how nine weeks of treatment are arranged.
About This Department
Ipilimumab was the first drug ever shown to lengthen life in metastatic melanoma. Paired with nivolumab, median survival reached six years.
Those figures come from the ten-year report of CheckMate 067. The same pairing now treats kidney cancer, melanoma that has reached the brain, bowel cancer with a DNA repair defect and several others, and it is also the hardest immunotherapy to tolerate, with serious side effects in half of patients or more. That trade is the subject of this page. Send us your pathology, molecular results and scans, and a medical oncologist will tell you whether the combination fits your cancer and your health.
Ipilimumab, an antibody, blocks CTLA-4. That brake acts earlier, and somewhere else, than the PD-1 brake that pembrolizumab and nivolumab block. The cards below show where it works. The list after them spells out what that difference means for a patient, from the number of doses to the organs most at risk and the absence of any test that predicts who will respond.
- Ipilimumab is almost never given alone now. Its value lies in partnership with nivolumab, and the few situations for single use are narrow.
- It is given briefly. Four doses three weeks apart in most regimens, after which nivolumab continues alone, or every six weeks alongside nivolumab in lung cancer and mesothelioma.
- The dose follows body weight. One or three milligrams per kilogram, depending on the cancer, so the amount of drug and its cost rise with weight.
- Its side effects come early. They hit the bowel and hormone glands hardest, and the serious ones cluster in the first three months, during the four doses, which is why the team watches that period more closely than any other.
- No test predicts who will benefit in melanoma or kidney cancer. The decision rests on the cancer type, the stage and whether the patient can withstand the side effects.
Dosing runs in two phases. The first sets the length of a stay abroad.
The older single-drug regimen
Before the combination, ipilimumab was given alone at 3 mg per kilogram for four doses. In the 2010 trial that established it, 676 patients with melanoma that had progressed on earlier treatment received ipilimumab, with or without a vaccine, or the vaccine alone. Median survival reached 10.1 months with ipilimumab alone and 6.4 months with the vaccine. No drug had lengthened survival in metastatic melanoma before. Grade 3 or 4 immune-related side effects occurred in 10 to 15 percent, and 14 patients, 2.1 percent, died of the drugs. PD-1 drugs have since replaced it as the first choice, and it is used alone today only in selected patients after other options.
Which cancers is it used for, and what did the trials find?
Six cancers appear on the European label, namely melanoma, kidney cancer, non-small-cell lung cancer, pleural mesothelioma, bowel cancer with a mismatch repair defect and squamous cancer of the esophagus, each treated with nivolumab alongside and in some with chemotherapy. The strength of the evidence differs a great deal between them.
Melanoma
Melanoma that has reached the brain
Kidney cancer
Bowel cancer with a DNA repair defect, lung, mesothelioma, esophagus
What are the side effects?
Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment.Conclusion of the first ipilimumab survival trial, New England Journal of Medicine, 2010
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
| Organ | What happens | How it compares with a PD-1 drug alone | What is done |
|---|---|---|---|
| Bowel | Diarrhea and colitis, from mild loose stools to bleeding and perforation | Far more frequent and more severe, the signature toxicity of ipilimumab | Steroids at once, infliximab or vedolizumab if steroids fail within days |
| Pituitary and other hormone glands | Headache, tiredness, low blood pressure, low sodium, from an inflamed pituitary. Thyroid failure or overactivity | Pituitary inflammation is characteristic of ipilimumab and rare with PD-1 drugs alone | Hormone replacement, often for life, and steroids for the acute phase |
| Skin | Itchy rash, sometimes widespread | More frequent | Creams, antihistamines, steroids for severe rash |
| Liver | Rising enzymes on the blood test | More frequent | Steroids, and treatment paused or stopped |
| Lung, heart, nerves, kidneys | Pneumonitis, myocarditis, nerve and muscle inflammation, nephritis | Similar or somewhat more frequent, rare but dangerous | Admission, high-dose steroids, specialist care |
Why the combination is harder to take
Treatment-related grade 3 or 4 adverse events occurred in 55 percent of patients, and one patient died of immune-related myocarditis.CheckMate 204, melanoma metastatic to the brain, New England Journal of Medicine, 2018
Half of patients on the combination, or more, have a serious side effect. Many stop before the fourth dose. That does not undo the benefit. In the melanoma trials, patients who stopped early because of side effects did as well as those who completed the course, because the immune response had already been set off. Nor do steroids, given properly and promptly, cancel the treatment. What undoes the benefit is a side effect caught late, when colitis has perforated the bowel or pituitary failure has caused a collapse, and the whole of the safety plan is built to prevent that.
Do steroids stop the treatment from working?
High-dose steroids given for an immune side effect do not, in the published analyses, reduce the chance that the cancer responds. Doctors start them without delay when the guideline calls for them, and tapered over four to six weeks, since stopping them too fast brings the side effect back.
- Blood tests before every dose, including thyroid, cortisol, liver, kidney, sugar and sodium.
- A diary of bowel movements during the four doses, and a same-day call for any rise.
- An alert card naming both drugs.
- Nothing started on your own.
- Follow-up of hormone levels for years, since pituitary and thyroid failure can surface late.
Hormone failure, the side effect that lasts
Most immune side effects resolve with steroids. Failure of the pituitary, thyroid or adrenal glands tends not to resolve, and the patient takes replacement hormones for life. Replacement works well, and life on it is normal, provided the patient knows to double the steroid dose in a fever or before surgery. The discharge letter spells that out.
Who it suits, how long to stay, and what decides the cost
Among patients alive and free of progression at three years, ten-year melanoma-specific survival was 96 percent with nivolumab plus ipilimumab.CheckMate 067 ten-year report, New England Journal of Medicine, 2024
The combination suits patients with melanoma or kidney cancer who are fit, without active autoimmune disease or an organ transplant, and willing to accept a high chance of a serious side effect in exchange for a better chance of long survival. It suits patients with melanoma in the brain who have no symptoms from it. Frail or elderly patients are harder cases, as are those with serious heart or bowel disease and those for whom a PD-1 drug alone offers a similar result with less risk. Patient and tumor board decide together.
Who should not receive it
Patients with an active autoimmune disease needing immune suppression, an organ transplant, uncontrolled infection including hepatitis B or C, pregnancy, and severe heart, bowel or liver disease are poor candidates. Earlier severe side effects from a PD-1 drug count against it. Each is weighed, and the reply to your file says plainly when we advise against it.
Grade 3 or 4 treatment-related events occurred in 46 percent with nivolumab plus ipilimumab and 63 percent with sunitinib, while discontinuation for adverse events was 22 against 12 percent.CheckMate 214, kidney cancer, New England Journal of Medicine, 2018
Send these five things.
- The pathology report, and the BRAF result for melanoma, the risk category for kidney cancer, or the mismatch repair result for bowel cancer.
- Staging scans with images, including a brain MRI.
- Every treatment so far, and any side effects from earlier immunotherapy.
- Blood tests with thyroid, cortisol, liver, kidney and hepatitis serology, and your weight.
- Any autoimmune disease, bowel disease, heart disease or transplant.
How long to stay in Istanbul
Nine to ten weeks.
That covers the four combination doses and the two weeks after the last one, when side effects are most frequent. Patients who can manage it stay for the whole phase in a hotel or apartment near the hospital, because a colitis or pituitary crisis is best recognized by the team that gave the drug. Others return every three weeks for each dose. Blood tests happen at home in between. Nivolumab maintenance continues at home, and a local oncology unit can give it from the written plan without any change to the drug, the dose or the interval. Fly at any point, provided no side effect is active.
What decides the cost
The drugs set the price.
Weight sets the ipilimumab dose, so a heavier patient receives more milligrams and pays more, and the combination phase adds nivolumab at each visit. Four combination cycles form most of the first-phase drug bill. Maintenance is separate. At home it costs less. Baseline scans, the blood tests before every dose, the day-unit time and the scan at twelve weeks are separate lines. An admission for colitis or hormone failure, with intravenous steroids and sometimes infliximab, is the largest unknown and should be priced in advance. Few hospitals in Istanbul publish a package for this combination, and quotes found online are nearly always for pembrolizumab, a different drug with a different schedule. Ask for three written figures. One per combination cycle, one per maintenance cycle, one for an admission. Your own figure follows the free review of your file.
Language, companions and follow-up once you are back home
One coordinator from the international patients team is assigned from your first message and stays with you through the combination phase. English, Arabic, French, Russian, Serbian, Romanian and Spanish are covered. Other languages are interpreted on request. An invitation letter naming the hospital and the treating oncologist goes out ten days before travel, with a longer visa requested for a stay of nine to ten weeks. The international patients office arranges the airport transfer, an apartment or hotel for you and a companion, and the rides to the day unit, and a companion is strongly advised for this treatment. Rooms for anyone admitted have a companion bed, a prayer room is on site, and halal, vegetarian and diabetic meals come from the hospital kitchen, while a request for a female doctor is passed to the department and met wherever the rota allows, which for a course of this length is a request worth making in the very first message. Back home, the coordinator stays reachable on the same WhatsApp number, the maintenance plan and the side-effect instructions go to your own oncologist, and hormone tests continue for years.
Ipilimumab FAQ
How does ipilimumab differ from pembrolizumab or nivolumab?
What is the success rate of ipilimumab with nivolumab in melanoma?
How often is Yervoy given?
What are the side effects of Yervoy?
How long do I need to stay in Istanbul?
Can my family come with me?
References
- Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine. 2010;363(8):711-723.
- Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. New England Journal of Medicine. 2025;392(1):11-22.
- Tawbi HA, Forsyth PA, Algazi A, et al. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. New England Journal of Medicine. 2018;379(8):722-730.
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine. 2018;378(14):1277-1290.
- Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology. 2018;36(17):1714-1768.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Metin GÜDEN, Radiation Oncology.
Medically reviewed by
Prof. Dr. Metin GÜDEN
Radiation Oncology
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