BY CYNTHIA DEMARCO
CAR-T cell therapy is a new type of cancer treatment offered at MD Anderson through clinical trials and FDA-approved standard of care cell therapy products. But what exactly is CAR-T cell therapy? And who should consider it?
We spoke with Sattva Neelapu, M.D., to learn more. Here’s what he had to say.
Let’s start with the basics. What is CAR-T cell therapy, and how does it work?
CAR-T cell therapy is a type of immunotherapy called adoptive cell therapy. Doctors extract T-cells (a type of white blood cell) from the patient’s blood and then add an artificial receptor (called a “chimeric antigen receptor”) to their surface. The receptor functions as a type of “heat-seeking missile,” enabling the modified cells to produce chemicals that kill cancer. And once we infuse them back into a patient’s body through an IV, they begin multiplying and attacking tumor cells.
CAR-T cell therapy can cause some unusual side effects. Tell me about them.
The most common side effect of CAR-T cell therapy is called cytokine release syndrome, or CRS. It’s also known as a “cytokine storm.” About 70-90% of patients experience it, but it’s very short-term and only lasts about five to seven days. Most patients describe it as having a severe case of the flu, with high fever, fatigue and body aches. It usually starts around the second or third day after the infusion. It happens because the T-cells have been multiplying and attacking the cancer, causing an immune response in the body.
There’s a very effective remedy for CRS now called tocilizumab, which reverses this side effect fairly quickly. The medicine was originally used to treat rheumatoid arthritis, but has since been approved by the U.S. Food and Drug Administration (FDA) to treat CRS.
The other side effect is known as “CRES,” which stands for “CAR-T cell-related encephalopathy syndrome.” It typically starts around day five after the infusion. Patients can become confused and disoriented, and sometimes may not be able to speak at all for a few days. CRES can be upsetting for patients and their families, but it typically lasts between two and four days, and it’s completely reversible. Patients eventually recover all of their neurological functions.
Which types of cancer can CAR-T cell therapy treat currently?
Currently, the FDA-approved CAR-T cell therapy products are used only for patients with adult B-cell non-Hodgkin’s lymphoma or childhood acute lymphoblastic leukemia who have already been through two unsuccessful standard treatments. But now clinical trials are starting to evaluate CAR-T cell therapy as a first line or second line of treatment for adult lymphoma and childhood acute lymphoblastic leukemia. We have different FDA-approved cell therapy products for each of these cancers, thanks to clinical trials.
Which cancers are being looked at for the next phase of CAR-T cell therapy clinical trials?
Indolent B-cell lymphoma, mantle cell lymphoma, multiple myeloma and acute myeloid leukemia.
Where do you see CAR-T cell therapy going in the future?
Right now, CAR-T cell therapy targets the CD-19 molecule on the surface of cancer cells. The reason it fails in some patients is that the tumor cells mutate quickly and shed the target molecule, so the CAR-T cells can’t “see” the cancer anymore. I expect future CAR-T cell therapy products to target multiple molecules: two, three or even more different molecules on a particular tumor. That would allow CAR-T cells to still recognize the cancer, even if one target molecule disappears.
Eventually, the hope is that CAR-T cell therapy could replace chemotherapy and stem cell transplantsaltogether. But first, we have to show that it’s at least as effective — or more effective — than those therapies. In fact, a new clinical trial was recently initiated to explore whether CAR-T cell therapy is more effective than an autologous stem cell transplant in adult diffuse large B-cell lymphoma.
What are some advantages of CAR-T cell therapy?
The major advantage is that CAR-T cell therapy is a single infusion that usually requires at the most two weeks of inpatient care, and then it’s done. In contrast, newly diagnosed non-Hodgkin’s lymphoma and childhood leukemia patients usually need at least six months or more of chemotherapy.
CAR-T cell therapy is also a living drug, and its benefits can last for many years. Since the cells can persist in the body long-term, they will still recognize and attack cancer cells if and when there’s a relapse. The data is still evolving, but after 15 months, 42% of adult lymphoma patients who received CD19 CAR-T cell immunotherapy were still in remission. And two-thirds of childhood acute lymphoblastic leukemia patients were still in remission after six months. These are patients whose cancers were deemed very aggressive and for whom other standards of care had failed.
What type of patient is a good candidate for CAR-T cell therapy?
Currently, a pediatric acute lymphoblastic leukemia or an adult aggressive B-cell lymphoma patient who has already been through two lines of unsuccessful treatment is ideal to receive CAR-T cell therapy. Until late 2017, there was no standard of care for someone who had already been through two lines of treatment and not achieved remission. CAR-T cell therapy is the only FDA-approved therapy to show significant benefit for those patients right now.
How easy is it for patients to obtain CAR-T cell therapy? Do they have to be on a clinical trial to access it?
Not necessarily. If they’ve already been through two lines of unsuccessful treatment, they can get the FDA-approved commercial product. But if they want it as first line or second line therapy — or want to use it for a different type of lymphoma — it would have to be through a clinical trial. Clinical trials have a limited number of slots available, and there can be a long waiting list. So, patients should ask their doctors early on about clinical trial options when they are considering treatment for their cancer.
What’s the one thing you want patients to know about CAR-T cell therapy?
This is a major breakthrough in the way we treat B-cell lymphoma and leukemia. And it’s offering hope to people who’d previously been given only about six months to live. The future looks much brighter now, as we identify mechanisms of resistance and develop more strategies to counteract them.
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