Our immune systems have the thankless jobs of guarding us from bacterial and viral invaders and preventing cancer development. Most of the time, we do not notice this hard work because the invaders are eliminated before they cause illness. However, certain immune cells can become cancerous themselves, disrupting the delicate immune system balance and leaving patients sick and vulnerable to pathogens. One type of immune cell cancer called large B-cell lymphoma (LBCL) occurs when B-cells grow and divide uncontrollably. Usually, B-cells produce infection-fighting proteins called antibodies, but when they become cancerous, they lose this ability. Even if LBCL responds to initial rounds of cancer treatment, the disease can still recur in patients.
To fight this recurrent disease, researchers are pitting immune cells against one another through the development of therapeutic tools called chimeric antigen receptor (CAR) T-cells. CAR T-cell therapy involves genetically engineering T-cells – which attack invader or mutated cells – to specifically target cancer cells that the normal immune system may have missed. CAR T-cells are very effective LBCL treatments, especially for patients like those with recurrent LBCL who do not respond to initial chemotherapy regimens. Due to their powerful cancer-killing activity, CAR T-cells can also cause major side effects like cytokine release syndrome (CRS), a condition that arises when a patient’s immune system overreacts to create whole-body inflammation. CAR T-cells can also attack healthy nervous system or blood cells on accident. All these side effects can be life threatening, so profiling the safety of CAR T-cell products is crucial to improving patient outcomes.
For LBCL, CAR T-cell therapies could cure roughly one third of patients experiencing cancer rebound after first-line chemotherapy has failed. Currently, two CAR T-cell products, axi-cel and liso-cel, are approved to treat recurrent LBCL. Because CAR T-cells are living and can persist in the body, they can continue to patrol and attack relapsed cancer cells, potentially making them more effective than other standard LBCL therapies. However, studies comparing the safety profiles of the two products are lacking. To address this gap in knowledge, a team led by Dr. Andrew Portuguese at Fred Hutchinson Cancer Center conducted a study to compare the safety and efficacy of the two products.