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.
Previous studies evaluated a limited number of patients (<100) and had a relatively short duration of follow-up (1 year). To expand our understanding of real-world outcomes, Portuguese and his team evaluated a larger group of patients and followed them for over three years. They found that axi-cel was associated with higher rates of CRS, nervous system toxicity, and blood system toxicity when compared to liso-cel. Additionally, patients that received axi-cel required more supportive care like immunosuppressive or antibiotic medications. They also required longer hospital admissions.
Despite the side effect disparity, the group found no significant differences in the patient response rates and long-term outcomes. Both drugs reduced the LBCL burden in patients by similar amounts. Overall survival and progression-free survival rates for both groups were similar, indicating that both drugs are effective options for treating recurrent LBCL.
The group hopes that the safety profiles of axi-cel and liso-cel characterized in this study will guide providers’ choices between the two products. For example, because liso-cel has a better safety profile, doctors may prefer to use that product in patients who are older or have underlying medical conditions. In the future, studies across multiple cancer centers with more patients and comprehensive follow up will be essential to confirm the results from this work and fully characterize differences between the two CAR T-cell products.
The spotlighted research was funded by the National Institutes of Health, Kuni Foundation, and Swim Across America.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Andrew Portuguese, Alexandre Hirayama, Lorenzo Iovino, Christina Poh, Ajay Gopal, Mazyar Shadman, Brian Till, Filippo Milano, Aude Chapuis, Folashade Otegbeye, Ryan Cassaday, Qian Wu, and Jordan Gauthier contributed to this work.
Portuguese AJ, Huang JJ, Jeon Y, Taheri M, Albittar A, Liang EC, Hirayama AV, Kimble EL, Iovino L, Poh C, Gopal AK, Shadman M, Till BG, Milano F, Chapuis AG, Otegbeye F, Cassaday RD, Basom RS, Wu QW, Maloney DG, Gauthier J. 2025. Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow up. Haematologica. doi: 10.3324/haematol.2024.287010
Kelsey Woodruff is a PhD candidate in the Termini Lab at Fred Hutch Cancer Center. She studies how acute myeloid leukemia cells remodel the sugars on their membranes to reprogram cancer cell signaling. Originally from Indiana, she holds a bachelor's degree in Biochemistry from Ball State University. Outside of lab, you can find her crocheting and enjoying the Seattle summers.
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