CAR T-Cell Therapy Advances in Large B Cell Lymphoma

On May 22nd, 2024, Dr. David Miklos, a lymphoma specialist at Standford Medicine, joined HealthTree for a webinar about CAR T-cell therapy advances in large B cell lymphomas. You can watch the recording or read the summary below.

Some major points from the webinar are as follows:

• CAR therapy's roots trace back to stem cell transplantation. This method involves replacing a patient’s diseased blood system with healthy donor stem cells and immune cells. However, these transplants come with significant risks, such as toxicity from high-dose chemotherapy and graft-versus-host disease, where donor cells attack the patient's body.
• CAR T-cell therapy involves modifying a patient's T-cells to target specific antigens on cancer cells. The first successful CAR T-cell treatments targeted the CD19 antigen found on B-cells, which are involved in various types of lymphomas and leukemias. These modified T-cells are collected, genetically engineered, expanded in a lab, and then infused back into the patient. Once in the body, they multiply rapidly and attack cancer cells.
• There are three FDA-approved CAR T-cell therapies targeting CD19: axicabtagene ciloleucel (Axi-Cel), tisagenlecleucel (Tisa-Cel), and lisocabtagene maraleucel (Liso-Cel). Each has shown significant success in treating relapsed (disease has returned) or refractory (not responding to treatment) lymphomas.
• Axi-Cel was the first tested CAR T-cell therapy in the ZUMA-1 trial, showing impressive results in patients with aggressive large B-cell lymphomas.
• More recently, the ZUMA-7 trial compared Axi-Cel directly with the traditional standard of care (high-dose chemotherapy followed by stem cell transplant) in second-line treatment for relapsed (disease has returned) or refractory (not responding to treatment) lymphoma. The study found that Axi-Cel was significantly more effective, with higher rates of progression-free survival and overall survival.
• CAR T-cell therapy is not without challenges. One common side effect is cytokine release syndrome (CRS), a flu-like condition that can cause high fever, low blood pressure, and difficulty breathing. 

During the Q&A session, the following questions were addressed:

• Do you anticipate that in the future creation of cellular therapies, you will have therapies that only target the cancerous B cells and not the healthy B cells, so you can avoid B cell aplasia as a long-term side effect? (timestamp 37:55)
• What is the CAR T-cell treatment regimen? (timestamp 41:12)
• Some studies show Axi-Cel is superior to Tisa-Cel in terms of efficacy and side effects. Can you tell us what you think about that? (timestamp 46:11)
• What do you think about the early prediction of cytokine release syndrome by measuring phosphate and magnesium? (timestamp 50:40)
• Do you find that CAR T-cell therapy is usually covered by insurance? (timestamp 52:48)

In summary, CAR T-cell therapy represents a monumental advancement in cancer treatment. It provides a personalized, potent, and durable response against aggressive lymphomas, offering new hope to patients who have exhausted other options. As research progresses, CAR T-cell therapy is likely to become an even more powerful tool in the fight against cancer, extending its benefits to more patients and types of cancer.

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