Yervoy (Ipilimumab)

What Is Yervoy?

Yervoy is the brand name of ipilimumab, an immunotherapy drug manufactured by the pharmaceutical company Bristol Myers Squibb.

Since its approval by the U.S. Food and Drug Administration in 2020, doctors have begun using Yervoy to treat adult patients with unresectable malignant pleural mesothelioma. Yervoy is currently only approved as a first-line mesothelioma treatment combined with nivolumab (Opdivo) for patients who do not qualify for surgery.

Yervoy is a monoclonal antibody and part of the immune checkpoint inhibitor drug class. It binds to the CTLA-4 protein to prevent immune suppression. For patients newly diagnosed with mesothelioma, doctors may prescribe Yervoy every six weeks with nivolumab every three weeks.

How Does Yervoy Work to Treat Mesothelioma?

Yervoy is a checkpoint inhibitor immunotherapy drug that increases the effectiveness of the body’s T cells.

T cells are white blood cells. They are part of the immune system that fights infections and cellular abnormalities such as cancer. Yervoy inhibits the CTLA-4 protein that blocks immune response, improving the ability of T cells to recognize and attack cancer cells. This mechanism increases your immune system’s natural defenses to help kill cancer cells.

Doctors administer Yervoy through an IV line in your vein or an access port. Pleural mesothelioma patients receive Yervoy every six weeks alongside Opdivo every three weeks for up to two years.

Many experts believe immune checkpoint inhibitors now provide a viable alternative to cytotoxic chemotherapy for eligible patients. Further improvements to this treatment will likely include advancements in cellular therapies and optimizing drug combinations to maximize benefits.

Yervoy Side Effects

The potential benefits of Yervoy are not without the risk of side effects. Some side effects, such as fatigue, are minimal and go away when treatment ends. Other side effects are more serious, such as the risk of developing nerve problems or colitis (inflammation of the colon’s inner lining).

Patients on Yervoy and Opdivo may experience side effects of one drug or both, which may differ from the side effects of Yervoy alone.

Pleural mesothelioma patients on combination therapy with Yervoy and Opdivo may have different reactions. Each immunotherapy drug has a list of potential side effects, and combination treatment can cause other unique adverse effects.

Bristol Myers Squibb cautions that the list of possible side effects may not be comprehensive. Patients receiving chemotherapy in addition to Opdivo and Yervoy commonly report constipation as an additional side effect. 

Treating side effects early minimizes the risk of long-term injury. Tell your doctor immediately if you notice any changes to your body while taking Yervoy so they can offer quick and effective treatment. Patients can also report side effects directly to the FDA by calling 1-800-FDA-1088.

Yervoy in Mesothelioma Treatment Research

Clinical trial results across many U.S. cancer centers have been promising and indicate that Yervoy is effective against mesothelioma when combined with Opdivo.

The CheckMate 743 clinical trial was instrumental in paving the way for Opdivo and Yervoy’s FDA approval to treat pleural mesothelioma. In April 2022, the study posted an update on its 605 pleural mesothelioma patients. Those treated with Opdivo and Yervoy had a median survival of 18.1 months compared to 14.1 months for chemotherapy alone.

In January 2022, the National Cancer Institute opened a clinical trial testing Yervoy with LMB-100, a protein engineered to kill cancer cells, for patients with unresectable malignant mesothelioma. After effective results in laboratory testing, the NCI opened the phase I trial to pleural and peritoneal mesothelioma patients.

The University of Chicago Medicine Comprehensive Cancer Center began enrolling patients in 2020 for a multimodal therapy trial examining the effects of Opdivo and Yervoy when added to peritoneal mesothelioma surgery.

In June 2017, French researchers announced the results of phase II clinical trials of Yervoy and Opdivo. All participants in the study had inoperable mesothelioma that had returned following one or two lines of chemotherapy with pemetrexed and cisplatin or carboplatin.

Approximately 50% of the 54 participants treated with the immunotherapy drug combination responded well. Tumors shrunk in nearly 26% of patients, and another 24% of patients showed no new tumor growth.

Results such as these are remarkable in the treatment of recurring mesothelioma. The cancer is known for its resistance to treatment, and these results have researchers excited about what future studies may hold for the mesothelioma community.

UV1 Vaccine with Opdivo and Yervoy

A 2020 phase II clinical research trial sponsored by Bristol Myers Squibb is testing the progression-free survival benefit of the UV1 cancer vaccine with nivolumab and ipilimumab in malignant pleural mesothelioma patients. Eligible patients must have disease progression after standard chemotherapy. Preliminary results are expected in 2022.

Yervoy in Combination with Novel Antibody

In 2017, researchers launched a phase II study testing the novel antibody INCAGN01867 with Opdivo, Yervoy and Opdivo plus Yervoy. The trial is targeting patients with advanced or metastatic malignancies, including mesothelioma. It was completed in November 2021, but early results are unavailable.

INITIATE Study

In 2016, researchers in the Netherlands launched a landmark trial called INITIATE to study the effects of ipilimumab and nivolumab as a second-line treatment on patients with malignant pleural mesothelioma.

The phase II study followed 33 patients with unresectable mesothelioma after disease progression following at least one previous line of platinum-based systemic therapy. Researchers completed the trial in 2019 and found that the combination therapy promoted T cell proliferation, while treatment with Opdivo alone did not.

MAPS2 Trial

MAPS2 was another clinical trial studying the effects of Opdivo and Yervoy as second-line therapy in pleural mesothelioma patients. MAPS2 launched in 2016 and enrolled 125 patients. At 12 weeks, 44% of patients on nivolumab achieved disease control compared to 50% in the nivolumab plus ipilimumab group.

The study successfully demonstrated anti-cancer activity without unexpected toxicity in relapsed patients with malignant pleural mesothelioma. Similar studies will likely lead to FDA approval for Opdivo and Yervoy as potential second-line treatments for mesothelioma patients.

What to Discuss with Your Doctor Before Taking Yervoy

It’s essential to discuss your medical history and any concerns with your doctor before taking Yervoy. For example, pregnancy is a severe contraindication, and Yervoy can harm your unborn baby. Patients on Yervoy should avoid breastfeeding during Yervoy treatment and for three months after the last dose.

Patients considering Yervoy should also provide a comprehensive list of their medications to their health care provider. Some drugs that bind to CTLA-4 can cause severe or fatal immune-mediated reactions. Potential drug interactions include certain vaccines (such as cholera), palifermin, Eliquis, Abraxane and Crestor.

Yervoy may cause complications in certain patients. Cytomegalovirus has been reported in patients with steroid-refractory immune-mediated colitis, a potential side effect of Yervoy. Ipilimumab should also be used cautiously in patients with a history of organ transplants, autoimmune disease or neurological disease.

Common Questions About Yervoy for Mesothelioma

Are Opdivo and Yervoy approved for mesothelioma?

Yes, the U.S. Food and Drug Administration approved Opdivo and Yervoy combination immunotherapy for first-line treatment of unresectable malignant pleural mesothelioma.

How do Opdivo and Yervoy work?

Opdivo is a checkpoint inhibitor that blocks PD-1, a pathway cancer cells use to hide from the immune system. Yervoy is a monoclonal antibody that targets cytotoxic T lymphocyte-associated antigen (CTLA-4), a protein that restricts the activity of the immune system. The medications are a potent combination that prohibit cancer cell protection and elevate T-cell activity.

What are the survival rates for Opdivo and Yervoy?

Results from a 2021 clinical trial of patients treated with Opdivo and Yervoy showed a median overall survival of 18.1 months, compared with 14.1 months for patients on chemotherapy. The two-year survival rate for patients on Opdivo and Yervoy was 41%, compared to 27% for the chemotherapy group.