Most doctors tend to be cautious about throwing around phrases and words like game changing and groundbreaking — particularly when it comes to cancer treatments. But CAR T-cell therapy, a type of immunotherapy, is offering hope where there was none before.
Last year, NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian/Columbia University Irving Medical Center began providing the novel therapy that genetically alters a patient’s own immune cells to fight cancer.
The approved CAR T-cell therapies are for adults with advanced large B-cell lymphoma and for children and young adults with the most common childhood cancer, acute lymphoblastic leukemia, known as ALL. For both blood cancers, the treatment is intended for patients who have not responded to standard treatments — chemotherapy and/or bone marrow transplantation — or whose cancer has returned after receiving the standard therapies. At that point, prospects for survival can be dire.
Though approved by the U.S. Food and Drug Administration for two types of cancer, CAR T-cell treatments for other cancers and life-threatening diseases are just a matter of time, experts say.
“Like the invention of radiation therapy, or the bone marrow transplant, or the first chemotherapy drugs, this could be the beginning of something quite spectacular,” says Dr. Koen van Besien, director of the Stem Cell Transplant Program at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian/Weill Cornell Medical Center.
“Clinical trials that are already active at our centers examine the utility of CAR T cells in other types of lymphoma, myeloma, and certain solid tumors such as pancreatic cancer, prostate cancer, and sarcoma,” adds Dr. Ran Reshef, director of translational research in the Blood and Marrow Transplantation Program and clinical lead for the CAR T-Cell Program at NewYork-Presbyterian/Columbia.
Here, Drs. van Besien and Reshef answer questions about CAR T-cell therapy, and discuss what this major stride means for the future of cancer treatment.
What is CAR T-cell therapy?
Dr. Reshef: It’s a type of immunotherapy, one that holds great promise in treating cancer. The major challenge with immunotherapy has been to find a way to improve the immune system so that it can do a better job of fighting cancer.
That’s what CAR T-cell therapy involves — collecting lymphocytes, also called T cells, from cancer patients, then sending the T cells to a lab to be genetically modified. I like to think of it as arming them to be able to recognize tumor cells. Once these newly armed T cells are manufactured, which takes two to four weeks, we infuse them back into the same patient so these cells can start attacking cancer cells.
Dr. van Besien: The CAR in CAR T-cell therapy stands for chimeric antigen receptor. With CAR T-cell therapy a patient’s T cells are implanted with a new receptor that makes the T cell super potent and able to recognize tumor cells. It’s a one-time treatment and, if all goes well, the T cells will expand and start attacking the lymphoma or leukemia, and the patient will achieve a complete remission. These T cells live and proliferate in the patient and continue to fight cancer. It’s a fantastic invention.
Why is CAR T-cell therapy considered to be such a huge advance?
Dr. van Besien: Simply put, it has the ability to eradicate large B-cell lymphoma and childhood acute lymphoblastic leukemia in patients where nothing else has worked. CAR T cells use a totally new mechanism of action. It’s a living drug, where the new T cells not only attack the cancer but also continue to multiply and persist in the patient.
Dr. Reshef: There is no question that using a patient’s own immune system to fight cancer is one of the major medical breakthroughs of the 21st century. What’s truly surprising is the tremendous potency of these re-engineered T cells. With a single infusion, these T cells destroy pounds and pounds of tumor. Someone coined the term serial killers to describe them, and I think that’s appropriate. These modified T cells move on to kill one tumor cell, then the next, and the next, to the very last one. As a result, patients who were once considered incurable are now going into complete remission for two years or longer. Some patients treated in the earliest clinical trials have now been in remission for more than eight years. It’s unprecedented.
What’s the process like for patients?
Dr. van Besien: Over two to three hours, an apheresis machine collects a patient’s blood, skims off the lymphocytes (or T cells), then returns the blood to the patient. The T cells then are shipped to the pharmaceutical company’s manufacturing facility to be genetically modified and proliferated. Two to three weeks later, the new T cells are sent back for infusion into the patient. Shortly before the infusion, patients receive a mild form of preparatory chemotherapy meant to reduce their own lymphocytes and make room for the new “super potent” T cells to establish themselves.
“There is no question that using a patient’s own immune system to fight cancer is one of the major medical breakthroughs of the 21st century. ”— Dr. Ran Reshef
What are some of the challenges?
Dr. Reshef: If all goes well, the patient recovers in the hospital or home after a single infusion of CAR T cells. The T cells will proliferate and start attacking the cancer cells. But roughly one-third of patients experience serious side effects that require acute management in the hospital, occasionally in intensive care. This occurs when the new T cells cause an aggressive inflammatory response in the patient. One side effect can be cytokine release syndrome (CRS), which causes shortness of breath, malaise, high fever, and a drop in blood pressure and oxygenation, among other symptoms.
Dr. van Besien: In addition to CRS, the inflammatory response can cause neurotoxicity, resulting in difficulty speaking, drowsiness, disorientation, and even coma. Not all patients experience this, but most will experience some of these side effects within the first two to four weeks of treatment. That’s why CAR T-cell therapy is reserved for the patients who have no other options and why it’s administered only in specialized centers, and only when the first-line treatments have failed. The good news is that the overwhelming majority of patients completely recover from these side effects.
Does CAR T-cell therapy work for everyone who receives it?
Dr. Reshef: In leukemia in children, it seems that between 60% and 70% will have a durable long-term response. In lymphoma cases, it seems that close to 40% of patients have a durable response for at least two years.
Dr. van Besien: We don’t know yet how many patients are going to be cured with CAR T cells. Patients who were involved in CAR T-cell studies were patients who had no chance with anything else. The studies show that almost half of the patients treated do very well. It seems quite powerful.
“Like the invention of radiation therapy, or the bone marrow transplant, or the first chemotherapy drugs, this could be the beginning of something quite spectacular.”— Dr. Koen van Besien
Where do you see CAR T-cell therapy going next?
Dr. Reshef: This is just the tip of the iceberg. We’re at a moment almost akin to the first chemotherapy treatments. We started with one type of chemo and now, five decades later, we have dozens of different chemotherapy agents. In the same way, there’s the potential for CAR T-cell therapy to expand and to be used for other cancers, as well as autoimmune diseases and inflammatory conditions. In the next three to five years, I think we’ll see the results of ongoing studies where CAR T-cell therapy is used to treat multiple types of blood cancers — and even solid tumors. At Columbia we have trials with CAR T cells and similar cell therapies for various types of lymphoma, myeloma, and certain solid tumors, including highly incurable cancers such as pancreatic cancer and sarcoma. I am very optimistic and hopeful that we will see treatment success in these trials.
Dr. van Besien: There is a trial here at Weill Cornell looking at CAR T-cell therapy for myeloid leukemia, where we use cells from a universal donor, off the shelf, so the therapy can be administered immediately, without the two-to-three week wait. I think we’ll continue to see variations like these. Another Weill Cornell trial that we are hoping to start soon is looking at CAR T cells to treat aggressive thyroid cancer. I’m usually a skeptic, but the therapy could be truly transformative. It’s quite a difficult treatment, but it’s just a matter of time before our science friends come up with tweaks that reduce the complications, expand its uses, and make it even more effective.
Ran Reshef, M.D., is director of translational research in the Blood and Marrow Transplantation Program and clinical lead for the CAR T-Cell Program at NewYork-Presbyterian/Columbia University Irving Medical Center. He is an associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.
Koen van Besien, M.D., Ph.D., is director of the Stem Cell Transplant Program and a professor of medicine at Weill Cornell Medicine, and an attending physician at NewYork-Presbyterian/Weill Cornell Medical Center. He specializes in the management of patients with recurrent lymphoma using stem cell transplant and cellular therapies.
Additional Resources
Learn more about CAR T-cell therapy at NewYork-Presbyterian.
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FAQs
How successful is CAR T-cell therapy? ›
What is the success rate of CAR T-cell therapy? In studies, 9 out of 10 people with acute lymphoblastic leukemia whose cancer didn't respond to other treatments or whose cancer came back had full remission with CAR T-cell therapy. Remission means the cancer can't be detected in tests.
Is CAR-T the future of cancer treatment? ›Chimeric antigen receptor (CAR)-T cell therapy is emerging as a promising option for patients with certain types of cancer. The advent of this immunotherapy has advanced the field of cancer care, but there are still many ways in which the therapy is being optimized.
What are the downfalls of CAR T-cell therapy? ›While the therapy can lead to long-lasting remissions for some patients with very advanced cancer, it can also cause neurologic side effects such as speech problems, tremors, delirium, and seizures. Some side effects can be severe or fatal.
Is CAR T-cell therapy better than chemotherapy? ›Recently, in two large clinical trials, CAR T-cell therapy proved to be more effective than the standard treatment for patients with non-Hodgkin lymphoma whose cancer returned after their initial, or first-line, chemotherapy.
Is CAR T-cell therapy a last resort? ›CAR T cell therapy was a last resort when other treatments failed. But now we're starting to prescribe CAR T cell therapy for some patients who've had only one type of treatment that failed to work. Early data from clinical trials suggest that CAR T cell therapy is better at treating some cancers than other therapies.
What is the failure rate of CAR T-cell therapy? ›As far as the CAR T-cell success rate goes, there are several studies to prove that this new approach is working: According to data provided by the Medical University of Chicago1, the CAR T-cell therapy success rate is about 30% to 40% for lasting remission, with no additional treatment.
How many patients have received CAR-T therapy? ›“At least 15,000 patients across the world have received CAR T cells, and dozens more clinical trials using this approach are in progress, for almost every major tumor type, but people in many parts of the globe still do not have access to treatment with these transformative therapies,” said Carl H.
Why is CAR-T therapy so good? ›CAR-T therapy works by taking some T cells (blood cells that help to protect you from infection and disease) out of your blood, genetically modifying them in a lab so they are much better at finding and killing cancer cells, and then putting them back into your blood to fight the cancer.
Do you lose your hair with CAR-T therapy? ›Will I lose my hair during CAR T-cell therapy? Patients who undergo CAR T-cell therapy typically do not lose their hair or experience some of the other common side effects of chemotherapy, such as nausea and vomiting.
How much does CAR-T therapy cost? ›The cost of treating CRS ranges from $30,000 to $56,000 per patient [28]. The total treatment cost for CAR T-cell therapy has been estimated to reach up to $500,000 for patients with severe CRS [28].
Is there an age limit for CAR T-cell therapy? ›
The FDA-approved conditions for CAR -T cell therapy include: B-cell precursor acute lymphoblastic leukemia (ALL), in people up to 25 years of age.
Who is a candidate for CAR T-cell therapy? ›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.
Is CAR-T covered by insurance? ›Many commercial health insurance plans pay for CAR T-cell therapy, but some may limit coverage and others may not cover it at all. Medicare covers CAR T-cell therapy. Medicaid coverage varies depending on the state in which you live.
What happens after CAR-T therapy? ›CAR T-cell therapy can affect your nervous system, causing symptoms that happen in the first few weeks after your treatment. Some symptoms can affect your ability to drive or operate machinery, so you should plan to avoid those activities for eight weeks after your treatment. Neurological symptoms include: Headache.
How long does it take to recover from CAR T-cell transplant? ›Recovery: Patients who receive CAR T-cell therapy have a risk/recovery period of approximately 2-3 months. During this period, patients will be evaluated for side effects and treatment response. It is not uncommon for patients to be admitted to the hospital during this period to manage complications.
Does CAR-T work for ALL cancers? ›Chimeric antigen receptors (CARs)
For example, in certain kinds of leukemia or lymphoma, the cancer cells have an antigen called CD19. The CAR T-cell therapies to treat these cancers are made to attach to the CD19 antigen and will not work for a cancer that does not have the CD19 antigen.
Cytokine release syndrome (CRS), a systemic inflammatory response caused by cytokines released by infused CAR T cells can lead to widespread reversible organ dysfunction. CRS is the most common type of toxicity caused by CAR T cells.
Can you do CAR T-cell therapy twice? ›VERY few patients have a more positive outcome from a second CAR-T infusion than from a first one. Some patients, though, may still wish to proceed with a second infusion, even with low odds of a positive outcome and despite the associated costs and risks.
Does Medicare pay for CAR-T? ›The Centers for Medicare & Medicaid Services (CMS) covers autologous treatment for cancer with T-cells expressing at least one chimeric antigen receptor (CAR) when administered at healthcare facilities enrolled in the FDA risk evaluation and mitigation strategies (REMS) and used for a medically accepted indication as ...
Why does CAR-T not work on solid tumors? ›“One of the main limitations is that most of the proteins present on solid tumors that could be used as targets are also found at low levels on normal cells, making it difficult to specifically direct the CAR T cells against tumor cells and spare healthy ones,” said presenter John Haanen, MD, PhD, a medical oncologist ...
Is CAR-T considered a transplant? ›
CAR -T cell therapy is not the same as stem cell transplant or chemotherapy. CAR -T cell therapy may be a treatment option for: Relapsed, refractory B-cell acute lymphoblastic leukemia.
What happens when patients are given CAR T cells? ›A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood.
When do CAR-T side effects start? ›Patients may experience fever, weakness, chills and loss of appetite. These side effects typically start a few days after the CAR T cell transfusion and last about a week.
How do you qualify for CAR-T? ›CAR T cell therapies have been approved for adult, pediatric, and young adult patients with certain relapsed or refractory cancers.
How long do CAR T cells persist? ›Researchers, as well as a patient who had chronic lymphocytic leukemia (CLL), hailed the findings as a cure, although more work needs to be done to see if the results persist in a larger group of patients.
Does Medicare cover T cell therapy? ›Medicare recipients will be able to receive coverage for this type of cancer therapy as long as they are provided in facilities that are approved by and enrolled in the FDA Risk Evaluation and Mitigation Strategies.
How long does a car t take to work? ›After about 3 months, the doctor will check to see if the CAR T cells worked. It's important to note that CAR T cells kill all cells against which they are directed, including normal cells. This usually results in a weak immune system for several months following treatment.
What does car t do? ›CAR T cell therapy is a type of cancer immunotherapy treatment that uses immune cells called T cells that are genetically altered in a lab to enable them in locating in destroying cancer cells more effectively.
How is CAR-T paid for? ›Put It All Together. Medicare pays for the administration of CAR T-cells in both inpatient and outpatient settings. Billing for outpatient CAR T-cell therapy includes HCPCS Level II codes for the therapies as well as coding for the administration.
Is CAR T-cell the same as stem cell? ›Summary: A stem cell transplant is a treatment option for some lymphoma patients who are at risk of relapsing after standard chemotherapy. CAR-T therapy is a new type of immunotherapy that is available to patients with B-cell lymphoma who relapsed or did not obtain a remission after standard chemotherapy.
How quickly do CAR T cells work? ›
The cell manufacturing process for this type of immunotherapy that was pioneered at Penn — CAR T cell therapy — typically takes nine to 14 days.
How long does it take for CAR T cells to work? ›When your CAR T-cells start to work, your immune system may respond by releasing large amounts of cytokines into your bloodstream. Most of the time, CRS happens in the first week or two after treatment.
How long does it take to recover from CAR T-cell therapy? ›Recovery: Patients who receive CAR T-cell therapy have a risk/recovery period of approximately 2-3 months. During this period, patients will be evaluated for side effects and treatment response. It is not uncommon for patients to be admitted to the hospital during this period to manage complications.
Does CAR-T work for all cancers? ›Chimeric antigen receptors (CARs)
For example, in certain kinds of leukemia or lymphoma, the cancer cells have an antigen called CD19. The CAR T-cell therapies to treat these cancers are made to attach to the CD19 antigen and will not work for a cancer that does not have the CD19 antigen.
The types of cancer that are currently treated using CAR T-cell therapy are diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, multiple myeloma, and B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients up to age 25.
Does CAR-T therapy make you lose your hair? ›Will I lose my hair during CAR T-cell therapy? Patients who undergo CAR T-cell therapy typically do not lose their hair or experience some of the other common side effects of chemotherapy, such as nausea and vomiting.
How long do side effects of CAR T-cell therapy last? ›Patients may experience fever, weakness, chills and loss of appetite. These side effects typically start a few days after the CAR T cell transfusion and last about a week.
What are the neurological side effects of CAR T-cell therapy? ›Neurological toxicity associated with CAR T-cell therapy, known as immune effector cell-associated neurotoxicity syndrome (ICANS), affects approximately 50 percent of recipients. Symptoms include confusion, delirium, aphasia, impaired motor skills, and somnolence.
How many patients have been treated with CAR-T? ›Right now, about 130 medical centers in the U.S. are even set up to offer the treatments, and it's likely that less than 2,000 patients have been treated, based on data provided by the companies that manufacture the two CAR-T therapies approved by the Food and Drug Administration.
Why does car T not work on solid tumors? ›“One of the main limitations is that most of the proteins present on solid tumors that could be used as targets are also found at low levels on normal cells, making it difficult to specifically direct the CAR T cells against tumor cells and spare healthy ones,” said presenter John Haanen, MD, PhD, a medical oncologist ...
Can CAR T cells treat solid tumors? ›
“Our work demonstrates that CDH17CAR T cells can eliminate solid tumors like NETs and GICs, but do not damage healthy, normal tissues that also express CDH17, because CDH17 is sequestered and hidden between the normal cells,” said senior author Xianxin Hua, MD, PhD, a professor in the Department of Cancer Biology in ...