In just a few years, therapies that boost the power of the immune system have become a mainstay of cancer treatment. Drugs that remove the “brakes” of the immune system have increased survival from some of cancer’s deadliest tumors, including melanoma and lung cancer.
Now immunotherapy is moving into the next stage of “living therapies.” These treatments manipulate the patient’s own T cells so they become more effective at finding, attacking, and killing cancer cells inside the body.
The first T cell therapy–CAR-T–was approved by the FDA on Aug. 30 to treat children and young adults who have a hard-to-treat form of acute lymphoblastic leukemia (ALL).
Pediatric oncologist Prakash Satwani, MD, associate professor of pediatrics at Columbia University Medical Center and the Herbert Irving Comprehensive Cancer Center, leads the CAR-T program at NewYork-Presbyterian Hospital/CUMC.
Q: How does CAR-T therapy work?
A: When a patient has cancer, the immune system is supposed to find the cancer cells and get rid of those cancer cells. But in some patients, that process does not happen.
When we do CAR-T cell therapy, we’ll get T cells from the patient, and then with the help of genetic engineering, train these cells to identify, attack, and kill leukemia cells.
The great thing about CAR-T cells is that when they see the target, they multiply inside the body. If there are a billion leukemia cells and we only infuse 50 million CAR-T cells, these CAR-T cells are going to expand when they see the leukemia cells. And then there should be enough to get rid of whatever leukemia cells are there.
Q: How will CAR-T therapy change the treatment of children with this type of leukemia?
A: CAR-T cell therapy is very exciting and has the potential to cure children with acute lymphoblastic leukemia, which at times is hard to cure, especially in cases when the disease comes back during the treatment or after the treatment. In these cases, patients tend to have a resistant leukemia and chances of a cure are less than 10 percent. In those cases, CAR-T cells are probably going to change the field.
So far, the experience has been very positive. Based on a few publications from Children’s Hospital of Philadelphia, at least 50 percent of the patients go into complete remission for a year after getting this therapy. It’s pretty much going from having no options to having a very good option available.
We have to wait for a few more years to get a full picture, but based on the encouraging results, it is very likely that these patients are not only in remission, but are cured as well.
Q: Why is CAR-T therapy only available in some medical centers?
A: One or two days after CAR-T cells are infused, there is a possibility that cytokine release syndrome will happen. The patient will become very hypotensive. That means that their blood pressure will go down, and in order for us to manage their blood pressure, we have to transfer them to the ICU.
Our ability to provide care to very sick patients is probably the reason we were chosen. We have a very large pediatric intensive care unit and a group of physicians who are very experienced in dealing with cytokine release syndrome, which happens in many different conditions. There are medications which can shut down the cytokine release syndrome, and we have experience in using those medications. We cure patients and save their lives.
Several of our physicians have now been trained by Novartis and most of the training has been to make sure everybody understands the risks associated with infusion of CAR-T cells, especially cytokine release syndrome and the neurological toxicities, and how to appropriately manage them. If we over manage the symptoms, there is a risk that we will kill the CAR-T cells and that will make them ineffective in a way that leukemia can come back.
Q: The therapy has only been approved for children with ALL who still have cancer after conventional treatment (chemotherapy and bone marrow transplant). Could the treatment be used earlier?
A: I think in the near future, bone marrow transplantations will be replaced by CAR-T cell therapies. The reason is that bone marrow transplant is associated with significant long-term issues. Once the child is cured, they have another 50, 60 years to live, and they will end up having a lot of long-term side effects from the bone marrow transplantation. CAR-T cells may have better cure rates and fewer issues with long-term toxicities than transplant.
Q: Can CAR-T therapy be used for other cancers besides acute lymphoblastic leukemia (ALL)?
A: There are ongoing studies where children with acute myeloid leukemia—those who have relapsed or have refractory disease—they hopefully will be getting CAR-T cells in the near future. CAR-T cells have been used for multiple myeloma and there have been some publications where it seems to be working well.
CAR-T cells seem to be effective for patients with diffuse large B-cell lymphoma, and it’s expected that CAR-T cells will get FDA approval for that indication down the road. There are various other investigators who have tried CAR-T cells for solid tumors. The results haven’t been that great when you compare it with acute lymphoblastic leukemia, but I’m sure the technology will get better in the near future.