Ipilimumab and pembrolizumab are two immunotherapy medications that harness the body’s immune system to combat cancer. When used together, they form a combination therapy that can be more effective than either drug used alone. This dual-action method empowers a patient’s own immune defenses against specific types of cancer cells.
How the Combination Works
The immune system’s T-cells act like soldiers that find and destroy threats, including cancer cells. However, cancer cells can evade this attack by activating natural “brakes,” or checkpoints, on the T-cells, which shuts down the immune response. This combination therapy works by releasing two of these checkpoints.
Ipilimumab is a monoclonal antibody that targets a checkpoint protein called CTLA-4. This protein acts as an early-stage brake, regulating the initial activation of T-cells in the lymph nodes. By blocking CTLA-4, ipilimumab allows for the generation and mobilization of a much larger army of T-cells to fight cancer throughout the body.
Pembrolizumab works on a different checkpoint known as PD-1. The PD-1 protein is found on activated T-cells and acts as a direct “off switch” when it binds to its partner, PD-L1, a protein often found on cancer cells. This interaction tells T-cells at the tumor site to stand down. Pembrolizumab blocks this PD-1 pathway, ensuring the T-cells remain active and can attack the tumor.
Using both drugs provides a two-pronged attack. Ipilimumab increases the number of T-cells available for the fight, while pembrolizumab ensures their attack is effective once they reach the tumor. This dual blockade has shown greater efficacy in certain cancers than targeting either the CTLA-4 or PD-1 pathway alone.
Cancers Treated With This Combination
The combination of ipilimumab and pembrolizumab is approved for treating several types of advanced cancers. One of the primary indications is for advanced melanoma, a form of skin cancer. For patients with metastatic or unresectable melanoma, this dual immunotherapy can lead to significant responses.
Another application is in the treatment of advanced renal cell carcinoma, the most common type of kidney cancer. For patients with this diagnosis, the combination therapy is often considered a first-line treatment option. The strategy aims to control the growth and spread of kidney cancer cells.
The use of ipilimumab and pembrolizumab also extends to certain types of non-small cell lung cancer (NSCLC). Its application in this context can be more specific, sometimes depending on the tumor’s expression of the PD-L1 biomarker. For some patients with metastatic NSCLC without certain genetic mutations, this combination may be an option.
The Treatment Process
Both ipilimumab and pembrolizumab are administered intravenously in a clinical setting. This method allows the drugs to enter the bloodstream and stimulate the immune system. An infusion session for pembrolizumab lasts about 30 minutes, while the schedule for the combination can vary.
A common treatment schedule involves administering both drugs on the same day to begin a treatment cycle. A patient might receive pembrolizumab with a low dose of ipilimumab every three weeks for four cycles. After this initial phase, treatment may continue with pembrolizumab alone as maintenance therapy, with infusions every three or six weeks.
The total duration of treatment varies based on the cancer type, patient response, and tolerance of side effects. Treatment may continue for up to two years, or until the disease progresses or side effects become unmanageable. The healthcare team monitors progress through scans and other tests to guide the treatment plan.
Managing Potential Side Effects
The enhanced immune response can also lead to the immune system mistakenly attacking healthy tissues, causing immune-related adverse events (irAEs). The risk of experiencing more frequent and intense side effects is higher with the combination compared to using either drug alone.
Common side effects involve the immune system attacking healthy organs. These can include:
- Fatigue
- Skin issues, such as a rash and itchiness
- Gastrointestinal problems like diarrhea or colitis (colon inflammation)
- Inflammation of the liver (hepatitis) or lungs (pneumonitis)
- Disorders of hormone-producing glands (endocrinopathies)
- Joint and muscle pain
Patients must report any new or worsening symptoms to their medical team immediately. Early reporting allows for prompt management and can prevent side effects from becoming severe. The primary management for these irAEs is corticosteroid medications, like prednisone, which suppress the overactive immune system to reduce inflammation.
In cases where side effects are severe or do not respond to corticosteroids, the immunotherapy may be paused or stopped permanently. Other immunosuppressive medications might be used for refractory cases. The medical team will weigh the benefits of continuing cancer treatment against the risks posed by the side effects.