CAR T cell therapy for multiple myeloma How does it work

CAR T cell therapy for multiple myeloma How does it work

CAR T cell therapy for multiple myeloma: How does it work? 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An emerging form of treatment is chimeric antigen receptor (CAR) T cell therapy. Multiple myeloma is a type of plasma cell neoplasm, a form of cancer that affects cells of the immune system. Currently, multiple myeloma is incurable. The natural progression of the disease means that people may have periods of remission followed by periods of active disease in a cycle. Other forms of the disease include relapsed myeloma, refractory myeloma, and even relapsed refractory myeloma (RRMM), which are particularly difficult to treat. CAR T cell therapy is a novel method of treating such diseases. It is highly specific and targets antigens, such as the B-cell maturation antigen (BCMA), that are present in myeloma cancer cells. Keep reading to learn more about how CAR T cell therapy can treat multiple myeloma, including how the therapy works, its effectiveness, its safety concerns, and its eligibility. What is CAR T cell therapy Share on PinterestTHOMAS COEX/AFP via Getty ImagesCAR T cell therapy is a type of immunotherapy that aims to modify the immune system’s response to cancer. The National Cancer Institute (NCI) says CAR T cell therapy is a type of treatment for blood cancers. Doctors may also use CAR T cell therapy for treating multiple myeloma in some people. CAR stands for chimeric antigen receptor, which is a special molecule that the therapy adds to a person’s T cells. T cells are a type of immune system cell. During the CAR T cell procedure, an individual’s T cells transform to recognize cancer cells and bind to antigens heavily present in them. This recognizing and binding feature facilitates the killing of cancer cells. Some of the CAR T cell therapies for multiple myeloma with approval from the Food and Drug Administration (FDA) include idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvytki). Eligibility for this therapy type The NCI states that the above FDA-approved therapies are only eligible for certain people. These include: children, young adults, and adults with B-cell acute lymphoblastic leukemia (ALL)adults with B-cell non-Hodgkin lymphomaadults with follicular lymphomaadults with mantle cell lymphomaadults with multiple myeloma Only Abecma and Carvytki have approval for use in cases of multiple myeloma. In all cases, CAR T cell therapy is currently not the first therapy of choice. Specialists only consider it when eligible individuals experience relapse or when past treatments, such as intensive chemotherapy, were unsuccessful. Doctors only approve FDA-approved CAR T cell therapies for people with relapses or disease progression through at least four prior cancer treatment options. Learn more about relapsed multiple myeloma here. Mechanism of action The process of CAR T cell therapy can take several weeks. Healthcare professionals administer CAR T cell therapy either in a clinic, hospital, or an oncology department. The process is:A medical professional inserts a needle into the individual’s arm to draw out blood into a tube. The tube pipe connects to an apheresis machine. This machine removes white blood cells, including the T cells. The remaining blood goes back to the individual’s arm via another tube.The specialist takes the sample to a laboratory, where they insert the CAR receptor into the T cells.The laboratory makes many copies, in the millions, of the now modified CAR T cell. The specialist uses a simple infusion to transfer the CAR T cells back into the individual’s blood.The CAR T cells bind to an antigen on the cancer cells and kill them. Doctors may give people chemotherapy before the CAR T cell infusion, so they may have a better chance of fighting their cancer. Effectiveness for multiple myeloma Research shows that CAR T cell therapy, specifically targeting BCMA, can be effective in treating people with multiple myeloma, even in those with advanced disease. By looking into twenty-three different CAR T cell products in 640 patients, the researchers found a pooled overall response rate of 80.5%. They also found that the median progression-free survival (PFS) was 12.2 months. The PFS relates to the length of time during and after treatment of the cancer that a person lives with the cancer and their condition does not worsen. The promising results show that this form of therapy has potential. However, further research and clinical trial data would be beneficial. The FDA only approved Abecma and Carvytki for multiple myeloma. It is important to note the rate of permanently curing people with multiple myeloma with these therapies is extremely low. Abecma A 2021 study summarizing the effects of a single infusion of idecabtagene vicleucel found the following from 128 patients: 73% of participants responded to this therapy type33% had a complete response or better, meaning that signs of a person’s cancer disappeared in response to treatmenta median duration response was about 11 months for all participants who responded to the therapy Carvytki Another 2021 study assessing 97 people taking a single infusion of cilta-cel, found the following:about 98% of participants responded to this therapy type, meaning that there was a reduction in their cancerabout 80% of participants showed a stringent complete response, which is a deeper level of response than a complete responsethe median duration of response was approximately 22 months Possible side effects The T cells bind to a protein, such as BCMA, which the cancer cells have in high amounts. This protein also exists in a tiny amount of healthy blood cells. This means that, theoretically, this therapy can limit the negative impact on healthy cells. However, that does not mean there are no significant downsides. The NCI reports that 99% of all trial participants for an Abecma study experienced some serious side effects. Common ones include:fatigueinfectionscytokine release syndrome, which is an overreaction of the immune systemhemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), which is similar to cytokine release syndrome and can be life threateningconfusionseizuretremorloss of speechdeliriuma low number of blood cells Three patients in the study experienced neurotoxicity — or brain side effects — that did not go away. Three also died. These side effects are also similar for Carvykti. The only difference was the addition of nerve pain and lower antibody levels. The study reported seven total deaths. Risks Some of the above side effects can be serious or fatal. The NCI mentions that both therapies come with boxed warnings for life threatening adverse effects, including HLH and MAS. If doctors recognize these effects early, they can treat them effectively. If not, they can lead to very low blood pressure and dysfunction in multiple organs. Some other warnings that accompany both products include:Cytokine release syndrome (CRS): This can cause symptoms, such as chills, breathing difficulties, nausea, and many others. Nervous system issues: This can cause symptoms, such as headaches, confusion, seizures, and many others.Low blood counts: This can cause symptoms of fatigue, bruising, and bleeding. It can also increase a person’s risk of infection. Carvykti also comes with two boxed warnings for Guillain-Barré syndrome and parkinsonism. These are conditions with symptoms similar to Parkinson’s disease, which might include tremors and slow movements. Furthermore, each therapy can take up to a month as scientists need to generate the CAR T cells from the individual’s blood and multiply them in the millions. Unfortunately, people with an aggressive or severe case of multiple myeloma may not have this time. CAR T cell therapy is not a lifelong cure for multiple myeloma or other blood cancers for most people. A 2021 study notes that most patients experience recurrence after a period of remission following treatment. Moreover, the cost for one infusion can be so expensive to be prohibitive, reaching up to $500,000. Summary Many treatments exist for people with multiple myeloma. Unfortunately, sometimes they do not work, and individuals must undergo consecutive treatments. When they do work, the remission period can be short, and the person may require maintenance drugs or other forms of treatment before their next therapy session starts. CAR T cell therapy is a new procedure that aims to lengthen the remission time between treatments. Two products have FDA approval, and their results are promising. However, they do come with serious side effects, and studies also report some deaths. The cost for each therapy session is exceptionally high. Hopefully, newer studies will continue reporting positive results, and make this therapy more accessible to everyone. Last medically reviewed on July 28, 2022Blood / HematologyCancer / OncologyMedically reviewed by Faith Selchick, DNP, AOCNP, Nursing, Oncology — By Stefano Iavarone on July 28, 2022 Latest newsWhat sets 'SuperAgers' apart? Their unusually large neuronsOmega-3 may provide a brain boost for people in midlifeSeasonal affective disorder (SAD): How to beat it this fall and winterCDC: Monkeypox in the US 'unlikely to be eliminated in the near future'Why are more women prone to Alzheimer's? 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