Last week, news of a brand new type of cancer treatment- known as CAR-T cell immunotherapy- flooded social media as well as every newspaper and TV news around the world. This breakthrough therapy was approved by the FDA marking an historic moment in cancer treatment. But why is this such big news? Is this new therapy thatgood? What makes it a breakthrough discovery? Can it be used for any kind of cancer? How affordable will it be? Let’s review the answers to this and other questions.

Cured from cancer in one month

It was 2012 when CAR-T cell therapy hit the public eye for the first time, when doctors used it on a six-year-old girl named Emily Whitehead who was suffering from a type of blood cancer named acute lymphoblastic leukemia (ALL).

After experiencing bleeding gums, bruises on her body and excruciating knee pain, Emily’s parents received the heartbreaking news- “it’s leukemia”. She had turned 5 years old just a few weeks before and now she was being diagnosed with cancer. She was supposed to have chemotherapy treatments for 26 months, but after just two chemotherapy session she developed severe infections in her legs. Doctors managed to get the infection under control without needing to amputate her legs and in about two months Emily got in remission. A year and a half later though, the cancer came back.

With her risks increasing and now given only a 30% chance of survival, doctors recommended a bone marrow transplant. The transplant required a full body radiation- which is known for its side effects which include infertility, long life learning disabilities, body growth and organ problems, among others. In a desperate search to avoid this, Emily’s parents got to Susan Rheingold, MD, a relapse specialist at the Children’s Hospital of Philadelphia (CHOP). She told them about the experimental therapy with CAR-T cells, but she also underscored that it was still not approved by the FDA for experimental trials. Emily’s parents enrolled her anyway in the phase I clinical trial. Meanwhile, Emily was treated with an aggressive chemotherapy, but the cancer didn’t go away. Sadly, doctors told her parents that there was nothing they could do anymore to save their daughter and suggested to enjoy the final days they would have with her.

As in a movie, that very same doctors at the CHOP got approval from the FDA to start CAR-T trial and a few days later the experimental therapy was dripped into Emily’s vein. One month later, she was declared cancer-free. Moreover, this year doctors declared her cured of leukemia because she has been cancer-free for five years.

Why is it considered a revolutionary treatment?

·     Kymriah– the name given to this new treatment by its producer Novartis- is thefirst gene therapy approved for cancer treatment. Yes, it is not a pill or an injection of man-made drugs, it is about modifying our genetic material in order to create super-efficient killer cells to target and destroy cancer cells. I have previously written about the existing fear of many people towards the words gene therapy or genetic manipulation, but when it is about relieving dying kids from the cancer nightmare then these words sound like the sweetest melody ever and of course an amazing advance in science. So, what gets to be genetically manipulated in Kymriah? The answer is the patient’s own blood cells- specifically a set of immune cells. They are taken out of their bodies, manipulated in the lab to make them super powerful to kill cancer cells and then re-infused to the patient’s blood in a single shot.

·     Since the treatment comes from the patient itself, this therapy is a significant step forward in individualized cancer treatment.

·     Kymriah has shown to be very effective against blood cancer when no other treatments seem to work, as I will explain further on.

·     The CAR-T cell therapy is targeted to the cancer, instead of blasting the body with poison that preferentially kills cancer cells but also a lot of healthy tissue, which in essence is what chemotherapy does leaving behind some pretty bad side effects.

How does the therapy works?

As I said, Kymriah is not a drug in the traditional sense, instead it is about an enhancement of our body’s own defending system against cancer. It is pretty much like putting our immune system on steroids.

So our bodies are actually armed with weapons to fight cancer, but the reason we not always win the battle is because cancer cells have found many ways to evade this weapons. Anyway, the complete army against cancer is our immune system, which also protect us from virus and bacteria that cause disease. The soldiers of this army are the immune cells with the main cancer fighters being our so called T cells, which can specifically detect cancer cells through some sort of anthenas- named antigen receptors- that are located in the T cells surface. What these anthenas actually detect are molecules or antigens that appear on the surface of the cancer cells, so when the anthenas latch to cancer cells it turns on the T cell soldier into a killer, which now releases toxic chemicals that damage the cancer cell, but also recruit other immune cells to the area to help eliminating the malignant cells.

In the CAR-T cell therapy, the patient’s own blood is extracted and the T cells are separated and then grown in the lab in a special environment with the necessary liquids and nutrients, which takes about 10 days. During this time, tens of millions cells expand into billions which means that the army against cancer is now going to be loaded with billions of killers.

With this large amount of soldiers, the genetic manipulation begins….. but why on earth do we need gene manipulation? Because those billion of potential killers have different sets of anthenas and thus can detect many other pathogens or aberrant cells, but we want to create an army of as many cancer-detecting killers as possible. It is all about giving them the right set of anthenas. So the gene for the chimeric antigen receptor specific for recognizing leukemia cancer cells in inserted into these T cell’s DNA and these cancer killers will then be injected to the patient’s blood.

(If you pay attention to this therapy name, CAR-T stands for Chimeric Antigen Receptor-T cells which means that this therapy uses T cells with a Chimeric anthena.)

Interesting statistics

The risk of getting ALL is less than 1 in 750; around 70% of those who get it will survive their leukemia for 5 years or more after they are diagnosed (which does notmean that people with ALL will only live 5 years). So, for a large number of people with ALL treatment may get rid of the cancer.

Treatment of ALL typically lasts for about 2 years. It is often intense, especially in the first few months of treatment and it includes Chemotherapy, Targeted therapy, stem cell transplant and in special circumstances other treatments may be used such as surgery, radiation therapy or monoclonal antibodies. If the leukemia keeps growing though or comes back after one kind of treatment, it is possible that another treatment might still cure it. If a person has tried many different treatments but the leukemia has become resistant to all of them, CAR-T cell therapy sounds like the very best alternative.

Although this specific CAR-T cell therapy, was approved by the the FDA exclusively for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse, the odds of getting better are very good. This first-in class therapy showed an 83% overall remission rate in this patient population with limited treatment options and historically poor outcomes. Pretty good!

How accessible and affordable is Kymriah going to be?

The price of Kymriah is $475,000 according to Bruno Strigini, CEO of Oncology at Novartis, but if the treatment does not work within the first month the patient would not be expected to pay. Price is very high, although cheaper than bone marrow transplants which can cost between $540,000 and $800,000.

Since patients who fit the criteria for treatment are under 25, they would likely be covered by insurance, because they would either be on their parent’s insurance or covered by government-sponsored Medicaid.

There is still a lot of research to do on the CAR-T cell therapy arena. Hopefully many other cancer targets- such as solid tumors- will be effective to treat in a near future. We are getting closer each time though.