Is CAR T-cell Therapy Possible for Myelofibrosis?

Could CAR T-cell therapy be a future option for people with myelofibrosis?

Learn what Dr. Alex Rampotas from University College London shared in a recent podcast about CAR-T’s potential to treat myelofibrosis. 

Listen to the Full Podcast

What is CAR T-cell therapy, and how does it work?

CAR T-cell therapy is a personalized treatment that uses a person’s immune system to fight cancer. CAR stands for “chimeric antigen receptor.” T cells are a type of white blood cell that are part of the immune system. In this approach, T cells are taken from the patient, modified with CAR in a lab to recognize cancer cells better, and then put back into the patient. These cells can then help fight the cancer. 

This treatment is already approved for certain blood cancers like B-cell lymphoma and leukemia. T cells are naturally good at detecting harmful cells, but cancer can hide from them. By giving T cells specific instructions through CAR technology, they can find and eliminate cancer cells more effectively. 

Dr. Rampotas and other researchers are studying ways to use CAR T-cell therapy for other blood cancers, but this depends on finding a clear target on cancer cells that healthy cells don’t have. That’s where the challenge for myelofibrosis comes in.

Why targeting myelofibrosis with CAR-T is more complex

For CAR-T to work, it needs a clear target on the surface of cancer cells. In B-cell cancers, it attaches to a well-known marker called CD19. 

In myelofibrosis, the cells don’t display a known target CAR-T can recognize without harming healthy blood-forming cells. Hitting the wrong target could damage the body’s ability to make blood, which would be unsafe.

To solve this, Dr. Rampotas looked for a more precise target. About a third of people with myelofibrosis have a mutation in the CALR gene. This gene produces a protein called calreticulin. The mutated calreticulin is on the surface of myelofibrosis cells, offering a target for the CAR T-cells. 

Promising early lab results

Dr. Rampotas and his team have tested CAR-T on calreticulin-mutated myelofibrosis in lab models and animal studies. The modified T cells could remove cancer cells while leaving healthy cells mostly untouched. Researchers also used 3D bone marrow models made from actual patient samples to test whether normal blood stem cells could still function after treatment.

So far, results show that the CAR-T successfully eliminated myelofibrosis cells and allowed healthy stem cells to continue making blood. These early results are important, but testing in humans is needed to understand long-term safety and effectiveness. 

When could CAR-T become available for myelofibrosis?

Although CAR-T-cell therapy for calreticulin-mutated myelofibrosis is still being researched in the lab, Dr. Rampotas aims to begin a phase one clinical trial within five years. This timeline depends on securing funding and regulatory approval.

A phase 1 trial focuses on safety and finding the right dose for patients. If early trials are successful, larger studies will be needed to test how well the therapy works. 

Which myelofibrosis patients might be eligible for CAR-T if trials begin?

At first, CAR-T would be available to patients with calreticulin-mutated myelofibrosis. If future research finds safe ways to target other gene mutations like JAK2 or MPL, more people could benefit. 

Dr. Rampotas noted that early trials may focus on patients who are unable to receive a stem cell transplant, such as seniors or patients with fewer matching donors. 

Knowing who might qualify helps people with myelofibrosis understand if this kind of treatment might be an option for them in the future. 

What are the potential side effects of CAR-T?

CAR T-cell therapy has known short-term side effects, including a strong immune reaction called cytokine release syndrome, which can feel like a very severe flu. Some people also experience short-term confusion or memory changes due to inflammation in the brain, called ICANS.

These side effects usually happen soon after treatment and are now better managed with supportive medicines. Long-term effects are still being studied. For example, CAR-T can sometimes weaken the immune system for a while in other cancers. Whether these effects would happen with CAR-T that targets calreticulin-mutated myelofibrosis is unknown. 

Is CAR-T a potential cure for myelofibrosis?

CAR-T aims to be a one-time treatment that not only eliminates cancer cells but also stays in the body to prevent them from returning. In other blood cancers, it has led to years of remission for some patients.

Reducing cancer cells with CAR-T could lead to fewer symptoms and a longer life in people with myelofibrosis. Whether CAR-T becomes curative is still unknown and will depend on future clinical trials. 

Looking ahead

CAR T-cell therapy for myelofibrosis is still being studied in the lab, but the research is encouraging. It offers a potential path for a more targeted and durable treatment for people with calreticulin-mutated myelofibrosis. Dr. Rampotas stressed that until this therapy is proven safe and effective, current approved myelofibrosis treatments remain the best path forward for most patients. 

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