CAR T-cell therapy, otherwise known as chimeric antigen receptor therapy, is a newly approved immunotherapy that specializes in altering the body’s T cells in a unique manner. FDA-approved medications include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta). Each drug has various differing indications of approved treatments ranging from leukemia, lymphoma, and multiple myeloma.
The extensive treatment process requires critical patient evaluations to determine eligibility.
Patients undergo leukapheresis in which white blood cells and T cells are collected from the patient, flowing into an apheresis machine. The apheresis machine returns blood back to the body through a different tube as it collects the required cells. The performing facility sends the collected cells to a laboratory to genetically modify the cells, placing chimeric antigen receptors on their surfaces. Over 2-3 weeks, the lab continues to grow the T cells as they multiply. Upon adequate multiplication and growth, the now-frozen cells are sent back to the performing facility. In the meantime, the patient may be given chemotherapy before CAR T cell infusion to improve the treatment efficacy of the CAR T cells. It is recommended not to give an intensive round of chemotherapy as some cancer cells are needed for attachment. The CAR T cell therapy is infused back into the patient where they are then monitored for several days for immediate potential side effects. Unfortunately, a severe response to the therapy may still be seen 2-3 months after administration of the therapy.
Many of the drug-approving clinical trials displayed high levels of remission in patients. For example, “ELIANA and ENSIGN studies showed a complete remission of 67% at 3 months in patients with acute lymphoblastic leukemia (ALL), which was maintained in almost 40% of patients after a median follow-up of 9 months. For non-Hodgkin’s lymphoma (NHL) patients, the objective response rate was 82%, with a 54% complete remission rate in 101 patients, after a minimum follow-up of 6 months.” These astonishing results came with high rates of severe side effects, especially cytokine release syndrome (CRS). CRS is seen due to an over-activation of the immune system and is associated with neurotoxicity. As seen in the ELIANA and ENSIGN studies, CRS and severe neurotoxicity were reported in 77.2% of patients. In another study, the ZUMA-1 study, CRS and severe neurotoxicity were reported in 13% and 28% of patients, leading to 2 deaths. The ROCKET trial had 5 deaths and ultimately led to its discontinuation. At the moment, research facilities are looking for methods to quickly and efficiently control potential cases of CRS in studies. Current approved treatment for grade 3 or 4 CRS includes tocilizumab, an IL-6 receptor inhibitor, and dexamethasone. Many facilities cannot differentiate between CRS and a severe infection, resulting in patients receiving preventative antibiotics as opposed to addressing CRS symptoms early on.
Unfortunately, such unique, specialized, newly approved medications come with a price in the world of cancer. Between biopsies, apheresis, CAR T cell engineering, hospital stays, imaging, and the medication itself, the cost ranges from $500,000 to $1,000,000. Other non-included costs are housing, travel, and caregiver support, as patients must stay at most 2 hours away for at least 4 weeks. In many instances, private insurances have covered a portion of costs. Medicare may cover the process of CAR T cell therapy in certain states, including everything except the drug itself. In instances where the medication is covered, it has been found to not cover the required supplies to perform the therapy. High response rates have been witnessed, however, the cost-effectiveness is controversial due to the excessive costs. Follow-up periods in trials were short as obtaining new evidence to support long-term efficacy and safety would be more costly. Over the past decade, immunotherapies have displayed great results in effectively treating cancer. Although the cost of CAR T cell therapy makes it not as accessible, the new category of ‘immunotherapy’ is now a standard first-line treatment in various cancers.
CAR T-cell therapy, otherwise known as chimeric antigen receptor therapy, is a newly approved immunotherapy that specializes in altering the body’s T cells in a unique manner. FDA-approved medications include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta). Each drug has various differing indications of approved treatments ranging from leukemia, lymphoma, and multiple myeloma.
The extensive treatment process requires critical patient evaluations to determine eligibility.
Patients undergo leukapheresis in which white blood cells and T cells are collected from the patient, flowing into an apheresis machine. The apheresis machine returns blood back to the body through a different tube as it collects the required cells. The performing facility sends the collected cells to a laboratory to genetically modify the cells, placing chimeric antigen receptors on their surfaces. Over 2-3 weeks, the lab continues to grow the T cells as they multiply. Upon adequate multiplication and growth, the now-frozen cells are sent back to the performing facility. In the meantime, the patient may be given chemotherapy before CAR T cell infusion to improve the treatment efficacy of the CAR T cells. It is recommended not to give an intensive round of chemotherapy as some cancer cells are needed for attachment. The CAR T cell therapy is infused back into the patient where they are then monitored for several days for immediate potential side effects. Unfortunately, a severe response to the therapy may still be seen 2-3 months after administration of the therapy.
Many of the drug-approving clinical trials displayed high levels of remission in patients. For example, “ELIANA and ENSIGN studies showed a complete remission of 67% at 3 months in patients with acute lymphoblastic leukemia (ALL), which was maintained in almost 40% of patients after a median follow-up of 9 months. For non-Hodgkin’s lymphoma (NHL) patients, the objective response rate was 82%, with a 54% complete remission rate in 101 patients, after a minimum follow-up of 6 months.” These astonishing results came with high rates of severe side effects, especially cytokine release syndrome (CRS). CRS is seen due to an over-activation of the immune system and is associated with neurotoxicity. As seen in the ELIANA and ENSIGN studies, CRS and severe neurotoxicity were reported in 77.2% of patients. In another study, the ZUMA-1 study, CRS and severe neurotoxicity were reported in 13% and 28% of patients, leading to 2 deaths. The ROCKET trial had 5 deaths and ultimately led to its discontinuation. At the moment, research facilities are looking for methods to quickly and efficiently control potential cases of CRS in studies. Current approved treatment for grade 3 or 4 CRS includes tocilizumab, an IL-6 receptor inhibitor, and dexamethasone. Many facilities cannot differentiate between CRS and a severe infection, resulting in patients receiving preventative antibiotics as opposed to addressing CRS symptoms early on.
Unfortunately, such unique, specialized, newly approved medications come with a price in the world of cancer. Between biopsies, apheresis, CAR T cell engineering, hospital stays, imaging, and the medication itself, the cost ranges from $500,000 to $1,000,000. Other non-included costs are housing, travel, and caregiver support, as patients must stay at most 2 hours away for at least 4 weeks. In many instances, private insurances have covered a portion of costs. Medicare may cover the process of CAR T cell therapy in certain states, including everything except the drug itself. In instances where the medication is covered, it has been found to not cover the required supplies to perform the therapy. High response rates have been witnessed, however, the cost-effectiveness is controversial due to the excessive costs. Follow-up periods in trials were short as obtaining new evidence to support long-term efficacy and safety would be more costly. Over the past decade, immunotherapies have displayed great results in effectively treating cancer. Although the cost of CAR T cell therapy makes it not as accessible, the new category of ‘immunotherapy’ is now a standard first-line treatment in various cancers.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954171/
https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
https://hillman.upmc.com/mario-lemieux-center/treatment/car-t-cell-therapy/fda-approved-therapies