Ipi (Yervoy) Nivo (Opdivo) Combination Therapy

Your questions answered about the Ipi (Yervoy) Nivo (Opdivo) Combination Therapy with Dr. Richard Joseph, MD.


My doctor is recommending the IPI/Nivo combination as my best shot at beating my stage IV melanoma.  I am thinking other options are out there?

The 2 primary treatments for patients with metastatic melanoma are immunotherapy and targeted therapy. Immunotherapy consists of either single agent anti PD-1 (pembrolizumab or nivolumab) or the combination of anti-PD1 and anti-CTLA4 (nivolumab and ipilimumab). The combination of nivolumab and ipilimumab appear to have highest rate of efficacy including a best response rate, (6% higher than single agent PD1) as well as the highest rate of survival, but it comes at the cost of the highest rate of toxicity. Trying to decide between the combination of ipilmumab and nivolumab versus single agent anti-PD1 is a difficult decision and must be discussed thoroughly between the patient and their treating oncologist.

Is the IPI (Yervoy) combined with the Nivo (Opdivo) or are they given separately?

The combination of ipilimumab and nivolumab are given during the same infusion session but not at the exact same time.

Can the dosage be lowered if I have problems with the treatment?

We typically do not lower the dose of immunotherapy, but rather hold the dose and wait for the symptoms to resolve and then restart the combination again. We typically do not lower the dose of immunotherapy but rather hold the dose and wait for the symptoms to resolve and then restart the combination again. There are centers that have reduced the amount of IPI however to lessen toxicity.

Will steroids block the effectiveness of the treatment?

This is a great question that the remains difficult to answer. Steroids are known to dampen the immune system and to treat over active immune systems. There is obviously a concern that giving steroids to a patient with immune therapy related side effects can block the effectiveness. With that being said, if the side effects from immunotherapy are severe, then steroids are appropriate. The goal of the steroid treatment is to give as little as necessary to treat the side effect.

What happens if I go off the IPI and just stay on the NIVO?  Will my odds go down?

Once a patient elects to go on the combination of ipilimumab and nivolumab they initially receive 4 doses of the combination and then repeat scans. If the scans show improvement then we typically recommend for the patient to continue with maintenance nivolumab. Not all patients will be able to tolerate all four doses of the combination, but it appears that patients who don’t receive all four doses and have to stop because of toxicity have similar outcomes to patients who complete all four cycles of the combination.

Is it true that if you have a lot of toxicity it means the combination is working better? And if I have an easy time it isn’t working?

This is a myth regarding toxicity and response. It might be true that patients who have toxicity have a slightly improved outcomes compared to those who don’t have toxicity but by no means does the presence of toxicity equate with success nor does the absence of side effects equate with lack of benefit.


Dr. Richard Joseph, MD, is an assistant professor of medicine/oncology at Mayo Clinic. His Hematology/Oncology fellowship was completed at MD Anderson Cancer Center. He is a voting member of the NCCN (National Comprehensive Cancer Network. He belongs to Melanoma International’s Scientific Advisory Board and received MIF’s Doctor of the Year award for 2015.