Yervoy and Mesothelioma

In 2020, the U.S. Food and Drug Administration approved Yervoy, also known by its generic name ipilimumab, as a new mesothelioma immunotherapy treatment option.

The FDA recommends treating physicians combine Yervoy with nivolumab (Opdivo) for mesothelioma as first-line therapy for pleural patients. Opdivo and Yervoy are in the same class of immunotherapy drugs and provide enhanced results when working together.

Pharmaceutical company Bristol Myers Squibb is the producer of both Opdivo and Yervoy. It funded the CheckMate-743 clinical trial that led to the FDA’s decision to approve Opdivo with Yervoy.

The median overall survival was 18.1 months for patients who received the Opdivo and Yervoy combination therapy in CheckMate-743. About 41% of Opdivo and Yervoy patients survived for two years or more. Patients on traditional platinum-based chemotherapy alone had a median survival of 14.1 months.

Pleural mesothelioma immunotherapy works by stimulating the patient’s immune system. Specific immune cells, such as T-cells, can find and attack cancer cells. These are the same cells that prevent infections by fighting viruses and bacteria. They also help develop antibodies against cancer and diseases.

Over time, immunotherapy restricts tumor growth by killing new cancer cells and preventing them from re-forming. Yervoy stimulates the immune system to produce more T-cells that can identify and regulate cancer.

Medications such as Yervoy and Opdivo are called immune checkpoint inhibitors. This group also includes pembrolizumab (Keytruda), another FDA-approved immunotherapy for mesothelioma.

Immune checkpoints prevent the body from exaggerating a response. They stop immune cells from attacking healthy tissues but also prevent those cells from fighting cancer. Checkpoint inhibitor drugs remove the restrictions that prevent T-cells from destroying cancer cells.

The immune system includes a checkpoint called CTLA-4 that decreases T-cell production when an infection has cleared. Malignant mesothelioma cells can send the CTLA-4 signal that tells the body more T-cells aren’t needed.

Yervoy deactivates this signal and allows T-cells to multiply and attack the malignant tumor. Because Yervoy improves T-cells’ destructive power, it pairs exceptionally well with Opdivo’s ability to unmask cancer.

Immunotherapy drugs such as Yervoy potentially benefit patients in more ways compared to traditional chemotherapy for mesothelioma, including:

Doctors have used Yervoy for several years, and the drug has benefitted patients with aggressive cancers such as melanoma, a type of skin cancer.

About 18% of late-stage melanoma patients live for five years or more after treatment with Yervoy. The five-year survival rate for patients who also qualified for surgery is over 65%.

In June 2017, a phase II clinical trial of Yervoy with Opdivo resulted in tumor shrinkage for 26% of mesothelioma patients. About 24% of patients had no signs of tumor growth throughout the multiyear mesothelioma clinical trial.

Mesothelioma patients must meet all of the FDA-approved indications for treatment with ipilimumab:

The recommended dose for ipilimumab is 1 mg per kg of the patient’s weight every six weeks until disease progression or unacceptable toxicity. The recommended dose of nivolumab is 360 mg every three weeks.

If there are no signs of worsening disease and the treatment is tolerated, patients can continue the combination therapy for up to two years.

Some side effects are relatively common among patients on immunotherapy for mesothelioma. Immunotherapy reactions are typically mild, however, and respond well to medication.

The most common side effects of Yervoy include:

Most patients can tolerate mild immunotherapy side effects. Doctors can also prescribe medications, such as diphenhydramine, to help with some minor reactions.

Yervoy and other immunotherapy medications can also cause changes in hormone levels, including in the thyroid. Doctors sometimes prescribe certain medicines to prevent problems such as hypothyroidism while on immunotherapy.

Many of Yervoy’s side effects are due to an inflammation reaction caused by swelling and irritation from the immune system. Long periods of inflammation can damage sensitive organs, causing more serious adverse effects.

More severe immunotherapy complications are rare, but organ dysfunction is possible in extreme circumstances. In the CheckMate-743 trial, severe adverse reactions occurred in 54% of patients receiving Opdivo with Yervoy. These complications include:

Early signs and symptoms of severe reactions may include chest pain, abdominal pain, increased heart rate, intestinal or urinary issues, low back pain and memory changes.

Mesothelioma cancer centers administer Yervoy as an intravenous medication through a port or vein. Infusion reactions sometimes occur with IV drug delivery. Possible IV complications include itching, rash, fever, dizziness or shortness of breath.

Patients interested in Yervoy should be aware of possible side effects and alert their doctor at the first sign of any new or changing symptoms.

In many cases, the benefits of Yervoy outweigh the risks. While there is still no cure for mesothelioma, Yervoy and other immunotherapy medications provide hope for mesothelioma patients. Innovative treatments such as Yervoy could be the first steps towards eliminating this terrible disease.