Dr Gordon on Managing Toxicities Associated With Liso-Cel in MCL

"There are 2 major things that we worry about: [CRS and neurologic toxicity]. Any neurologic event can be a scary event for patients and families because…they're very noticeable for everybody."

Leo I. Gordon, MD, Abby and John Friend Professor of Oncology Research, professor, medicine (hematology and oncology), Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, discusses the management of toxicities associated with lisocabtagene maraleucel (liso-cel; Breyanzi) in patients with mantle cell lymphoma (MCL).

CAR T-cell therapy is associated with distinct toxicities that require careful monitoring, such as cytokine release syndrome (CRS) and neurologic toxicity, Gordon begins. CRS typically occurs within 2 to 5 days post-infusion and affects at least half of patients, he says, adding that most cases are mild, presenting as transient fever and responding well to acetaminophen and intravenous fluids. Occasionally, CRS involves low blood pressure, and rare cases may require intensive care for blood pressure stabilization, Gordon notes. Severe CRS is uncommon but underscores the importance of close observation in the early days following CAR T-cell infusion, he states.

Neurologic toxicity, also referred to as immune effector cell-associated neurotoxicity syndrome (ICANS), often develops later, typically between days 5 and 8, Gordon continues. It can present in a variety of ways, ranging from mild cognitive changes, such as subtle forgetfulness, to severe complications like encephalopathy or seizures, which occur in a small percentage of patients, he details. Mild symptoms occur in approximately 30% of patients and are generally self-limited, resolving within a day or two with corticosteroid treatment, Gordon reports. These can be identified using simple bedside assessments like memory recall or counting tasks.

Severe neurologic events, such as grade 3 or 4 toxicity, are rare, affecting approximately 3% to 5% of patients, but may necessitate intensive care, Gordon says. To monitor for early signs, many centers implement daily cognitive assessments, asking patients to recall their name, location, or perform tasks like counting backward, he expands. Seizure prophylaxis is commonly used, which may contribute to the low incidence of seizure-related complications. Neurologic toxicity can be alarming for patients, families, and clinicians due to its unpredictable nature and visibility, emphasizing the need for proactive monitoring and multidisciplinary management, Gordon emphasizes.

Although CRS and neurologic toxicity are generally manageable, their occurrence can be distressing for patients, families, and providers, highlighting the importance of proactive monitoring and prompt intervention. However, these events are generally manageable and rarely overshadow the significant therapeutic benefits of CAR T-cell therapy, Gordon concludes.