Immunotherapy for Melanoma: Where We Are

As was reported last week, Former President Jimmy Carter has melanoma that has spread to other organs, and part of his treatment will include an immunotherapy drug. Immunotherapy is a term used to describe treatments that harness the body’s immune system to fight cancer cells. Several of these are approved by the FDA for treating melanoma, including the one Mr. Carter is getting, and newer ones are in the pipeline.

How Does Immunotherapy Work?

Using your immune system to fend off cancer sounds natural and appealing, right?  After all, the immune system helps to combat other diseases like infections, so why not cancer, too? Doctors have been trying for decades to take advantage of the ability of immune cells to distinguish between healthy normal tissue and diseased cancer tissue. Unfortunately, only recently has this worked well in cancer.

It turns out that in patients with melanoma, component cells of the immune system have been fooled into ignoring the melanoma. How does this happen? Certain molecules act as “checkpoints” to prevent attacks on healthy cells and turn off a potentially over-eager immune response to minimize autoimmune disease (when the body attacks and destroys healthy body tissues by mistake). Melanoma cells take advantage of this regulatory step and turn on checkpoint signals that let them avoid being detected by the immune system. It’s like Harry Potter and his cloak of invisibility or Klingon Warships with the same…pick your metaphor. The melanoma cells subvert checkpoint signaling to essentially become invisible and avoid being killed by the immune system.

A truly profound change in recent years is the advent of certain immunotherapy drugs that target and block these checkpoints, which increases your body’s immune response. Without the checkpoint signal, the immune cells can do their job of recognizing the tumor as foreign. In this way, immunotherapy drugs activate the immune system to invade tumors and attack melanoma cells.

Patients receive checkpoint inhibitor immunotherapy drugs intravenously (into a blood vein). They are systemic, which means that the treatments travel through the bloodstream to reach all parts of the body. Cancer physicians use systemic immunotherapy to treat metastatic cancer, which is cancer that has spread from its original location to other areas of the body.

What Immunotherapy Drugs are Used for Melanoma?

Since 2011, the U.S. Food and Drug Administration (FDA) has approved three immunotherapy drugs:

  • Yervoy® (Ipilimumab),an anti-CTLA-4 antibody, approved in 2011
  • Keytruda® (Pembrolizumab), an anti-PD-1 antibody, approved in 2014
  • Opdivo® (Nivolumab), an anti-PD-1 antibody, approved in 2014

The anti-PD-1 immunotherapy drugs in particular are showing promise for other types of cancer, too. In fact, earlier this year, the FDA approved nivolumab to treat a certain type of lung cancer.

What’s Next for Immunotherapy Drugs?

The approvals of these immunotherapy treatments have come at an amazing pace and along with targeted therapies the melanoma treatment landscape is dramatically improved compared to just 5 years ago. Unfortunately, the current treatments don’t yet offer a universal cure. The gains are significant and unprecedented – make no mistake.  But some tumors are resistant to treatment and new approaches must be developed to overcome the limitations.

Now, researchers are trying to understand how to tailor the treatments to maximize results for more patients. And history teaches us that using active drugs in unique combinations often works well in cancer. So, some of what we’re trying to understand now include questions like:

  • What are the optimal combinations that balance good activity and good tolerability
  • What is the best order to give these therapies to patients
  • How long should patients be treated for the best results
  • Which patients will most likely benefit from certain drugs or combinations

The European Commission recently approved nivolumab and pembrolizumab for treatment of patients with advanced metastatic melanoma, including in the first-line treatment of the disease. In the US, the FDA is considering this same indication for each drug, as well as the combination of nivolumab and ipilimumab. FDA decisions are expected by the end of 2015.

With anti-PD-1 drugs first approved just last year, these expanded uses clearly demonstrate the remarkable pace of advances for melanoma patients around the world and the hope for even better outcomes for patients in the months and years to come.


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