The U.S. Food and Drug Administration (FDA) recently expanded the approval of Kymriah™ (tisagenlecleucel) to include adults with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma. Kymriah™ offers another treatment option for people with DLBCL whose disease is refractory (it hasn’t responded to other treatments) or relapsed (it has come back after treatment), and experts are excited about this potential life-saving therapy.1
In CAR T-cell therapy, the person’s own T-cells are removed from the blood. Then, using an inactive virus, the T-cells are modified to produce a specific receptor on the surface of their cells, called a chimeric antigen receptor (CAR). This receptor recognizes and attaches to a specific protein found on the blood cancer’s cells.3 Kymriah™ modifies the T-cells to attach to the CD19 protein on B-cell lymphoma cells.4 The modified T-cells are then replicated in the laboratory to create hundreds of millions of copies. These engineered T-cells are then infused into the patient, where they find and kill the cancer cells in the body.3
The process is individualized and creating the modified T-cells may take approximately 3-4 weeks. Before receiving the CAR T-cell therapy, patients may receive chemotherapy to reduce the number of cancer cells circulating in the body. The infusion of the CAR T-cell therapy generally takes less than an hour. Patients are advised to stay close to the hospital where they received treatment for at least four weeks in case of serious side effects.5
Another treatment option for diffuse large B-cell lymphoma
Approximately 50% of people with DLBCL experience their disease returning (relapse) or becoming refractory, where it becomes resistant to treatment.6 People with refractory DLBCL have poor prognoses (expected outcome). Research shows refractory DLBCL has a low response rate to additional therapy: 8% have a complete response and 18% have a partial response to subsequent therapy.4,7
Previously, patients with refractory DLBCL have not had many options that offered much hope of putting their disease into remission or giving them more time. The approval of Kymriah™ offers these patients another option. As Dr. Stephen J. Schuster, professor and director of the Lymphoma Program at Penn’s Abramson Cancer Center said in a statement, “Many lives may be saved.”1
Efficacy and safety of Kymriah™ in people with diffuse large B-cell lymphoma
The FDA gave the approval based on clinical trial results of Kymriah™ in DLBCL. The study was called JULIET and recruited patients from around the globe. The efficacy data included 68 patients, and results showed 50% had some response with 32% having a complete response (their disease was undetectable or considered in remission) and 18% having a partial response.2
Side effects that occurred in more than 20% of patients who received Kymriah™ included cytokine release syndrome, infections, fever, diarrhea, nausea, fatigue, low blood pressure (hypotension), swelling in the arms or legs (edema), and headache.2 Cytokine release syndrome (CRS) is a potentially serious inflammatory side effect that can lead to death if not treated promptly. The symptoms of CRS include fever, chills, difficulty breathing, dizziness or lightheadedness, nausea, vomiting, diarrhea, a fast or irregular heartbeat, and severe fatigue or weakness. Patients who experience any of these symptoms should immediately seek medical care.8
Urciuoli B. FDA approves CAR-T cell therapy for diffuse large B-cell lymphoma. Cure Today. Available at https://www.curetoday.com/articles/fda-approves-cart-cell-therapy-for-diffuse-large-b-cell-lymphoma. Accessed 5/9/18.
FDA expands approval of Kymriah to include relapsed or refractory large B-cell lymphoma. Healio. Available at https://www.healio.com/hematology-oncology/lymphoma/news/online/%7B6907d61c-5cc5-4b95-a2c7-3c4b5464f90f%7D/fda-expands-approval-of-kymriah-to-include-relapsed-or-refractory-large-b-cell-lymphoma. Accessed 5/9/18.
CAR T cells: engineering patients’ immune cells to treat their cancers, National Cancer Institute. Available at https://www.cancer.gov/about-cancer/treatment/research/car-t-cells. Accessed 5/9/18.
Narasimhan V. Novartis CTL019 – JULIET data on DLBCL, Investor call. Available at https://www.novartis.com/sites/www.novartis.com/files/2017-06-ir-call-ctl019-dlbcl-juliet-presentation.pdf. Accessed 5/9/18.
Kymriah product website, Novartis Pharmaceuticals. Available at https://www.us.kymriah.com/acute-lymphoblastic-leukemia-children/interested-in/treatment-information/. Accessed 5/9/18.
Crump M, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017 Oct 19;130(16):1800-1808. doi: 10.1182/blood-2017-03-769620. Epub 2017 Aug 3.
Crump M, Et al. Outcomes in refractory aggressive diffuse large b-cell lymphoma (DLBCL): Results from the international SCHOLAR-1 study. Journal of Clinical Oncology 2016 34:15_suppl, 7516-7516.
Kymriah prescribing information, Novartis Pharmaceuticals. Available at https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kymriah.pdf. Accessed 5/9/18.