Lifesaving CAR-T Therapy May Carry Small Risk of Blood Cancer, FDA Says

Fact checked by Nick Blackmer

Key Takeaways

• The FDA is investigating the cause of new blood cancers in some patients who received CAR-T therapy.

• While scientists have long suspected that the gene therapy could cause T-cells to become malignant, there have been no suspected cases of that happening until now.

• Experts say it’s not yet clear that CAR-T is responsible for the secondary cancers and that the benefits of CAR-T still outweigh the risks of the treatment.

The Food and Drug Administration (FDA) is investigating some cases in which a lifesaving cancer treatment may be the cause of new cancer, the agency said Tuesday. 

Approved in 2017, CAR-T therapy has been considered a game-changer for treating life-threatening blood cancers including lymphoma, some forms of leukemia, and multiple myeloma in patients who have not achieved remission through chemotherapy and other standard treatments.

Now, the FDA said it has received reports of new lymphoma cases in 20 patients who received CAR-T therapy. The agency is investigating the risk in all six CAR-T products in the class.

Tens of thousands of people have now received CAR-T cells. If the lymphoma cases identified by the FDA prove to be caused by T-cells modified by CAR-T therapy, that cancer risk would be far less than 1% of the adverse events of the treatment.

How CAR-T Works

To give CAR-T therapy, clinicians remove white blood cells called T-cells from a patient’s blood and genetically modify them to make proteins called chimeric antigen receptors (CAR), which help the T-cells to attack cancer cells. Those genetically modified T-cells are infused back into the patient’s blood.

A Surprising Finding

Scientists in the field have long known that genetically modified T-cells could theoretically be transformed into a cancer cell, said David Porter, MD, director of Cell Therapy and Transplant at Penn Medicine Abramson Cancer Center. Whenever someone injects a cell with new genetic information, there is a possibility that it could turn certain genes on or off in such a way that the cell becomes cancerous.

Still, Porter told Verywell the FDA report was “somewhat of a surprise.” Of the several hundreds of patients his team has treated over the past decade, he said there hasn’t been a single case of new blood cancer after CAR-T treatment.

“The potential benefit [of CAR-T] is great when you have no other treatment options and are likely to die of your cancer. Meanwhile, we think that the potential risk for something like a T-cell lymphoma has to be quite low,” Porter said. “From what we know today, the benefits still greatly outweigh what small risk there may be from getting a T-cell lymphoma.”

Related: CAR-T Therapy May Treat Conditions Other Than Blood Cancers, Research Shows

What We Know About These Cases

The FDA has not shared detailed information about the reported cases. The agency said that the reports of secondary cancer came from clinical trials and adverse events data systems—anyone who receives modified T-cells is enrolled in a rigorous, 15-year follow-up study to look for possible long-term effects.

To test whether CAR-T therapy is responsible for causing the secondary blood cancers, scientists will remove some of the T-cells from the patients and test whether there is any genetic material from CAR that played a role in turning the T-cell into a cancer cell.

Weighing CAR-T Risks and Benefits

More than half of CAR-T treatments result in years-long remission.

“The vast majority of patients who are receiving commercial CAR-T cells have far advanced, high-risk cancers. Many have exhausted all conventional standard treatment options,” Porter said. “CAR-T has really revolutionized this field. It’s being given to patients who have no other options, who would likely die of their disease fairly quickly, and yet it’s inducing remissions and long-term remissions in many of these patients.”

But as with most aggressive treatments, CAR-T often carries risks, said Michael Bishop, MD, a professor of medicine and Director of the Hematopoietic Stem Cell Transplantation Program at the University of Chicago.

Bishop said there is an estimated 5% risk of dying from some complication of CAR-T. If there is indeed a risk of secondary blood cancer from CAR-T, he said that risk would likely be small enough not to change the risk-benefit calculus.

“The inherent benefit far outweighs that risk,” Bishop said. “We have to take it seriously, but also have to put it in perspective.”

Conventional blood cancer treatments—like chemotherapy, radiation, and bone marrow transplants—can damage DNA and cause mutations that can lead to cancer.

The risk of developing a secondary cancer with chemotherapy and radiation is “markedly higher” than the suspected risk from CAR-T, Bishop said.

Related: Differences Between a Primary Cancer and a Secondary Cancer

Because most patients who receive CAR-T cells have already been treated with multiple rounds of chemotherapy and radiation, they may already be susceptible to developing new cancers or succumbing to cytokine release syndrome or neurotoxicity, Bishop said.

“[Patients] should be knowledgeable of this risk as well as others, such as infection risk and other secondary malignancies, are a possibility and that they should review this very, very carefully with their physicians,” Bishop said. “But I would hope that it would not keep them from seeking this potentially lifesaving therapy.”

What This Means For You

There is little public information about the cases of secondary cancers reported to the FDA, and it’s too soon to know whether those cases arose as a direct result of CAR-T. If you are considering the treatment, speak with a trusted oncologist or other medical expert about the risks and benefits of CAR-T.

Read the original article on Verywell Health.