Is Immunotherapy Right for Me?

Immunotherapy is a genuine game changer. For the first time, there’s a treatment for melanoma that can extend or even save lives. Former President Jimmy Carter credits one of these drugs for making the melanoma that had spread to his liver and his brain seem to vanish.

Despite the good news, these drugs don’t work for everyone with melanoma. Scientists are hard at work to figure out why and pinpoint the differences between patients who respond and those who don’t.

Here’s something else to think about before you try them: It’s rare, but the cure may be worse than the disease. Immune therapy can affect other organs and organ systems. Your doctor will take all this into account before she puts you on this type of treatment.

How Does Immunotherapy Work?

The drugs approved to treat metastatic melanoma activate killer T-cells, the white blood cells that are your immune system’s version of foot soldiers. Because the tumors started out as normal cells before they turned cancerous, the immune system doesn’t realize that they’re the ones causing trouble. If it did, it would swing into action and stop them. The new drugs help your body spot and fight cancer cells better.

Known as checkpoint inhibitors, they flip molecular switches on the surface of immune cells and unlock the brakes on your immune system. The first one, ipilimumab (Yervoy), helps T-cells recognize cancer cells as foreign to the body. Nivolumab (Opdivo) and pembrolizumab (Keytruda) boost your immune system’s response to cancer cells.

Is It in Your Genes?

One reason why they may work better for some people than others: Doctors think tumors that have the most DNA damage are more likely to respond to these drugs. This makes sense: The mutant molecules stick out on the surface of the tumor cell, making it easier for the immune system to recognize them as foreign. 

This means the drugs may work best with melanomas caused by too much DNA-damaging UVA sunlight.  These findings could lead to diagnostic tests that identify which patients are most likely to benefit from these therapies.

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Then again, there isn’t a direct cause and effect at play. Generally, the more mutations you have, the better your response will be. But not always. Some people don’t have a lot of genetic mutations but respond well. Scientists believe that other -- and as yet undiscovered -- checkpoints may be the cause.  

Or your immune system may need a little more help spotting cancer cells so it can destroy them. Pairing these immune-based anticancer drugs, like a mix of ipilimumab and pembrolizumab, might work better. Studies showed a good response rate, and doctors got the FDA’s OK to use the combo in 2015.

There’s still some guesswork involved in figuring out who will respond best. Doctors don’t want to withhold what could be a life-saving treatment, so they’re more willing to try the drugs and watch you closely to see if they can help.

Serious Side Effects

These drugs fire up your immune system, which can lead to other problems. They can cause inflammation that gives you sore joints or bouts of diarrhea. For most people, steroids can help manage the symptoms and not stop the drugs from working.

Checkpoint inhibitors can also take a toll on your endocrine system and can slow down vital secretions from the pituitary, adrenal, or thyroid glands. In addition to steroids, you might have to take permanent hormone supplements after being on this type of treatment.

If you’re taking immune-suppressing drugs because you had an organ transplant, or you have an autoimmune condition like rheumatoid arthritis or Crohn’s disease, the jury is still out. Doctors need to do more research before they know for sure if these drugs will harm or help.

WebMD Medical Reference Reviewed by Stephanie S. Gardner, MD on December 12, 2018

Sources

SOURCES:

Memorial Sloan Kettering Cancer Center: “New Findings Clarify How Immunotherapy Works -- and Why, In Some People, It Doesn’t,” “Understanding Jimmy Carter’s Surprise Cancer Turnaround: A Conversation with Jedd Wolchok.”

UpToDate: “Toxicities associated with checkpoint inhibitor immunotherapy.”

Dana-Farber Cancer Institute: “What Is a Checkpoint Inhibitor: Immune Checkpoint Inhibitor Definition,” “What Are the Side Effects of Immunotherapy?”

Pharmacy and Therapeutics: “Ipilimumab (Yervoy) Prolongs Survival in Advanced Melanoma.”

American Cancer Society: “Immunotherapy for melanoma skin cancer.”

News Release, FDA.

The New England Journal of Medicine: “Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma,” “Genetic Basis for Clinical Response to CTLA-4 Blockage in Melanoma.”

Siwen Hu-Lieskovan, MD, PhD, oncologist, UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

Medscape: “How to Treat Side Effects of New Cancer Immunotherapies.”

Journal for ImmunoTherapy of Cancer: “Ipilimumab in patients with melanoma and autoimmune disease.”

European Journal of Cancer: “Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient.”

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