Investigational CAR- Therapies and the side effects caused by cytokine release syndrome (CRS) Can I take other at the same time as • What is the that I will be receiving prior to the CAR T cell therapies that target CD19, CD20, CD22, and CD30 are unique to CAR T cell therapy. CAR T cell therapy? CAR T cell therapy? • What is the goal of this treatment? What are the expected are in development for patients with lymphoma and chronic Before receiving the CAR T cell therapy, tell your healthcare Is the procedure covered by insurance? benefits? lymphocytic (CLL). provider about all the medications, including the dosages, you Before undergoing this procedure, check with your medical currently take. Be sure to include prescription and over-the- • Will I require bridging therapy? If so, what type? Several CAR T cell therapies, including lisocabtagene maraleucel insurance provider to see what costs the provider will cover and counter medicines, as well as vitamins and herbal supplements. • How will we know if the CAR T therapy is working? What tests (JCAR017), are in clinical trials including the use of currently what costs you will be responsible for paying. The medical center It is also important to tell your healthcare provider about all your will I need to determine if treatment is working, and how often FDA approved CAR T cell therapies and its use in other subtypes performing the procedure usually submits all of the required of lymphoma. There are also second generation CAR T cell medical history, including if you have or have had: will I need to be tested? information to determine if your insurance will cover these • therapies, in early phases of clinical trials, such as dual targeted procedures. If there is a dispute about coverage or if coverage • Neurologic conditions (such as seizures, stroke, What are the risks and possible side effects of each treatment? CAR T therapy and allogeneic CAR T cell therapy. For the most is denied, ask your insurance carrier about their appeals process. or memory loss) Can these side effects be prevented or controlled? recent information on approved CAR T cell therapies, visit If a claim is repeatedly denied, contact your state’s insurance • Lung or breathing conditions • How will this treatment affect my normal daily activities (work, lymphoma.org/CART. agency. CAR T cell therapy should only be performed at • conditions driving, childcare, etc.)? certified centers, which may require travel and lodging near the • Liver conditions • What should I do to take care of myself during and after treatment center. Be sure to consider these costs and ask your The Benefits of Participating in a • Kidney conditions treatment? provider if they cover these expenses. Clinical trials are not a “last resort” for patients. Every drug • A recent or active infection • Will I still be able to work? available today had to be tested in clinical trials before it was If you need financial assistance, talk with your doctor and social • Do I need a caregiver while I am in treatment? CAR-T Cell Therapy approved for general use, and all new and emerging treatments worker about available options to enroll in an appropriate • Are there any medical conditions that would exclude me from for lymphoma and chronic lymphocytic leukemia/small program. organizations like the Lymphoma Research Questions to Ask Your Doctor lymphocytic lymphoma (CLL/ SLL) must be tested this way getting CAR T cell therapy? Foundation (LRF) offer limited financial assistance to patients • Would CAR T cell therapy be a good treatment option for me? before patients can use them in the future. Participating in a who qualify. Some pharmaceutical companies may have patient • What is a clinical trial? Are clinical trials available that are for Lymphoma Would choosing this treatment prevent me from getting a clinical trial can help to improve treatment options for patients assistance programs in place that help to provide drugs to different kind of treatment at a later point? studying new treatments for my type of NHL? Would a clinical for many years to come. Clinical trials offer both benefits and qualified patients, as well. trial be appropriate for me? How would I benefit? risks. Patients in clinical trials may be able to try new treatments manipulates that are not otherwise available to all patients. However, this For additional information on financial aid resources, view new treatment may or may not be more effective than the LRF’s Resources for Financial Assistance fact sheet available at the power of a patient’s immune standard therapy. At the very least, patients who are randomized lymphoma.org/publications or contact the LRF Helpline at to the control group will receive the standard therapy that they (800) 500-9976 or [email protected]. system to attack tumors. An would have received if they had not enrolled in the trial. The health of the patient enrolled in a clinical trial is monitored Which symptoms should I call my healthcare Review Committee immunotherapy approach, called very carefully. provider about or go to the emergency room? Clinical trials are crucial in identifying effective drugs and You will need to seek immediate attention for any of the Medical Reviewers Lymphoma Research chimeric antigen receptor (CAR) Foundation Reviewers determining optimal doses for patients with lymphoma. following: Jeremy S. Abramson, MD T cell therapy, uses patients’ Patients interested in participating in a clinical trial should view • Signs or symptoms associated with CRS including fever, chills, Massachusetts General Hospital the Understanding Clinical Trials fact sheet on LRF’s website at Uchenna Esomonu fatigue, rapid heartbeat, nausea, feeling short of breath, and Support Services Coordinator own immune cells to treat www.lymphoma.org, talk to their physician, or contact the LRF feeling faint or dizzy upon standing. Nancy Bartlett, MD Helpline for an individualized clinical trial search by calling • Signs or symptoms associated with neurologic events Washington University School of Medicine Victor Gonzalez their cancer. 800-500-9976, completing LRF’s online clinical trials request including altered mental state, sleepiness, memory loss, Associate Director of Support Resources and Ann S. LaCasce, MD form, or emailing [email protected] or personality changes, seizures, changes in your level of Strategic Partnerships consciousness, difficulty writing, speech disorders, tremors, Harvard Medical School, Commonly Asked Questions and confusion. Dana-Farber Cancer Institute Izumi Nakano • Signs or symptoms associated with infection such as fever Associate Director of Support Services How is CAR-T cell therapy different from stem cell Michael Wang, MD or chills. MD Anderson Cancer Center Sarah Quinlan transplantation? • Signs or symptoms associated with suppression Senior Director of Programs and Strategy Both stem cell transplantation and CAR T cell therapy are including feeling overtired, bleeding that does not stop, Helpline cellular therapies, and many of the steps in the procedures are or fever. similar, such as collecting cells from the patient (or a donor), (800) 500-9976 conditioning chemotherapy, and reinfusion of the cells. How can I be sure that I am getting my own CAR T [email protected] However, CAR T cell therapy and stem cell transplantation differ 9:30am to 7:30pm EST in many ways. An autologous transplant is not immunotherapy cell therapy? Lymphoma (promoting the body's own immune response), but rather There are several quality control checks throughout the process (Monday - Friday) gives a patient autologous stem cells (their own stem cells) or to make sure that you only receive your own CAR T cells. Your Supported through unrestricted grants from: CAR T Cell allogeneic stem cells (from a family member or unrelated donor) T cells are labeled with a unique identifier that stays with them Website to rebuild their immune system after chemotherapy. Patients during the entire process, and the identifiers are carefully who undergo allogeneic transplant receive stem cells from a matched to your identity before the cells are infused. lymphoma.org donor which is an immunotherapy designed to have a new immune system recognize and attack a patient’s lymphoma cells. How long do I need to be near the certified Allogeneic transplant patients also require immunosuppressants treatment center? to control rejection of the new immune system (“graft”) or experience graft-versus-host disease, where the new immune You will need to plan to be near the certified treatment center system attacks the patient’s healthy cells. Since the CAR T cells (usually within 50 miles) for at least four weeks after the infusion of your CAR T cells. are your own genetically altered cells, your body should not © 2020 Lymphoma Research Foundation reject these new cells, nor should they attack healthy cells other Information contained herein is the property of the Lymphoma than those expressing the CAR T cell target. Additionally, the Research Foundation (LRF). Any portion may be reprinted chemotherapy prior to CAR T cells is generally less intense than or reproduced provided that LRF is acknowledged to the chemotherapy prior to transplants, with fewer side effects, be the source and the Foundation’s website (lymphoma.org) is included in the citation. Because of the potential of these side effects, you should not After Receiving the CAR-T Cells drive or engage in hazardous occupations or activities, such as The Process After receiving the CAR T cells, you may need to remain in or operating heavy or potentially dangerous machinery, for at least near the certified treatment center for at least four weeks to eight weeks after the procedure. be monitored for side effects and treated, if needed. Some Neurological symptoms are treated with corticosteroids and patients can receive their CAR T cells as an inpatient with close anti-seizure medications such as levetiracetam, if needed. surveillance in the clinic. If it is done as an outpatient, you will need to have a caregiver, as you may not feel able to care for 1 Leukapheresis 4 Lymphodepleting yourself and it is not safe for you to be alone for the first few Other Side Effects weeks after the infusion. Hypersensitivity reactions can occur during the infusion, The first step of CAR T cell therapy is to obtain some of your T cells, Chemotherapy which is a condition where the body has an exaggerated a type of white blood cell. White blood cells work as part of the immune Side effects from CAR T cell therapy usually range from mild to response to a foreign agent that can trigger a strong reaction Chemotherapy moderate in severity. Severe, life-threatening reactions are rare, A few days prior to your CAR T cell infusion, you will receive 3 to 4 by the body. Other side effects may include severe or system to help the body fight infections. but may be experienced by some patients. Be sure to ask your consecutive days of chemotherapy as an outpatient. The two drugs life-threatening infections, reactivation of hepatitis B viral This process is called leukapheresis and usually take about three healthcare team which side effects you should contact them infections, low white blood cell counts, and low platelets. Blood Cells T Cells most commonly given prior to CAR T cell infusion are fludarabine to four hours. about, and when to call 911. If there is any question of what you As with many anticancer treatments, secondary malignancies and cyclophosphamide. are experiencing after receiving treatment, then it is important are also possible. • During leukapheresis, your blood is often removed through a to always contact your healthcare team. • The purpose of the chemotherapy is to suppress the immune central line in which a catheter is inserted underneath your collar system slightly so that the immune system does not inhibit your LRF’s award-winning Focus On Lymphoma mobile app Long-Term Side Effects bone, referred to as “pheresis catheter”. Sometimes, CAR T cells once they are infused. (lymphoma.org/mobileapp) and Lymphoma Care Plan In most patients, the number of CAR T cells increase to an intravenous (IV) line may be used instead. (lymphoma.org/publications) can help patients manage a maximum level within two weeks then steadily decline. • This gives the CAR T cells the chance to grow and expand • Your blood is then passed through a machine that separates your documenting treatment side effect when speaking with your However, CAR T cell therapy is unique in that the genetically to fight your lymphoma. healthcare team. modified cells can stay in your body for years, even if all lymphocytes, included T cells, from the other blood cells. Your T cells the tumor cells are gone. Other normal healthy cells in your are then isolated from the other cells. Side Effects body can also be attacked and be killed by your CAR T cells; • The rest of your blood cells are returned to your body through for example, healthy B cells also express CD19 and are the pheresis catheter or an IV line inserted in the other arm. Cytokine Release Syndrome (CRS) also killed by CAR T cells targeted to CD19. This results in Cytokine release syndrome (CRS) is your body’s response to temporarily having low levels of healthy B cells. Low B the activation and growth of your CAR T cells. When the CAR T cells also leads to decreased levels of healthy antibodies, cells attack the lymphoma cells, white blood cells are activated also called immunoglobulins, which can increase the risk and release inflammatory chemicals called cytokines. Cytokines of infection. This may be treated with the administration are part of the natural inflammatory response a person might of immunoglobulins to help keep you protected 5 CAR T Infusion have after a severe infection. However, a sudden release of a against infections. large quantity of cytokines can be very serious and does require 2 T-Cell Engineering A day or two after completing chemotherapy, you will receive CAR T Cells treatment by your doctor. CAR-T Cell Therapies in Lymphoma your CAR T cells at your certified treatment center. This can be • The symptoms can include flu-like symptoms, fever, low blood The apheresis product containing your lymphocytes are sent to a done either as an inpatient or as an outpatient depending on the pressure, and body aches. Approved CAR-T Cell Therapies* processing center (lab) where the T cells are separated from the facilities available at your treatment center. • CRS usually occurs in the first few days to two weeks after the Axicabtagene Ciloleucel (Yescarta) rest of the cells, and then are genetically engineered to target your • The infusion of CAR T cells takes less than one hour. infusion of the CAR T cells. • Treatment targeting CD19 for patients with certain types of lymphoma. A genetically engineered T cell means that the genes of CAR • Side effects will be treated with medications and other large B cell lymphoma who have not responded to or who that particular T cell are modified or changed in order that the T cell T Cell • You may be given acetaminophen (Tylenol) and/or diphenhydramine supportive treatments in the hospital. Rarely, CRS can be so have relapsed (cancer has returned after treatment) after at is “re-programmed” to fight the lymphoma. (Benadryl) before the infusion to prevent allergic reactions to the severe that patients require care in an intensive care unit least two other kinds of treatment. preservative in the CAR T cell product. and very rarely may even need to be placed on a breathing − Diffuse large B-cell lymphoma (DLBCL) not otherwise • This genetically enhanced cell now has chimeric antigen receptors machine temporarily or need temporary dialysis. specified (CAR) that allow the T cells to recognize your cancer cells. Chimeric Genetically • One used to treat CAR T cell-induced CRS is − Primary mediastinal large B-cell lymphoma antigen receptors are proteins that are on the surface of the cell. Engineered T Cell tocilizumab (Actemra), which was approved by the U.S. Food − High grade B-cell lymphoma • The CAR on the surface of the T cells binds (attaches) to a specific target and Drug Administration (FDA) in 2017. Corticosteroids can also be given for severe symptoms. − DLBCL arising from follicular lymphoma (for instance CD19) that are on your lymphoma cells. Once bound to a Brexucabtagene Autoleucel (Tecartus) cancer cell, the CAR activates the T cell to attack the lymphoma cell. Neurological Effects • Treatment targeting CD19 for adult patients with relapsed or Neurological effects may occur between two days and three refractory mantle cell lymphoma (MCL). This is the first CAR T 6 weeks after receiving the CAR T cells, and usually follow CRS. cell therapy approved for the treatment of MCL. CAR-T Cell Attack These may include: Tisagenlecleucel (Kymriah) • Anxiety • the Lymphoma • Treatment targeting CD19 for patients with certain types of Delirium (a temporary mental state of confusion, reduced large B cell lymphoma who have relapsed or were refractory Once the CAR T cells enter your body, they begin to multiply CAR T Cells Attack awareness of your environment, etc.) Lymphoma Cells (cancer does not respond to treatment) to two or more lines 3 CAR T-Cell Transport and attack the lymphoma cells. • Dizziness of systemic therapy. Lymphoma • • It is important to remain closely observed by your healthcare Headache − DLBCL not otherwise specified • The engineered T cells are then grown at the processing center for team so that you can be monitored for side effects. Insomnia (difficulty sleeping) − High grade B-cell lymphoma roughly two weeks. The goal is to produce millions of these cells. • Seizures (rare) − DLBCL arising from follicular lymphoma Once enough of the CAR T cells are available, the cells are frozen • Speech conditions (difficulty speaking) *Neither axicabtagene nor tisagenlecleucel can be used in patients for transport to your certified treatment center. • Tremor (shaking) with primary central nervous system lymphoma. CAR T Cells The precise cause of these symptoms is unknown, but they appear related to effects of the cytokines within the central nervous system.