Monitoring, Management Strategy Reduces CAR-T Neurotoxicity in Multiple Myeloma

Movement and neurocognitive treatment-emergent adverse events occurring after chimeric antigen receptor (CAR) T-cell therapy in patients with multiple myeloma declined after the implementation of strategies to monitor and manage those events, according to a recent study.

Adam D. Cohen, MD, of the Abramson Cancer Center at the University of Pennsylvania, and colleagues conducted the study and published its results in Blood Cancer Journal. The paper’s senior author is Sundar Jagannath, MD, of the Mount Sinai Medical Center.

While CAR T-cell therapies are “highly effective” for multiple myeloma, their “impressive efficacy is associated with treatment-related neurotoxicities in some patients,” Dr. Cohen and colleagues wrote. For example, movement and neurocognitive treatment-emergent adverse events occurred in 5% of patients with multiple myeloma who received ciltacabtagene autoleucel in CARTITUDE-1, they noted.

The study evaluated the factors associated with movement and neurocognitive treatment-emergent adverse events by assessing neurotoxicity data from 97 patients in CARTITUDE-1, with a median follow-up of 18 months.

Patients who experienced these events were characterized by the presence of a combination of at least two of the following variables: high tumor burden, grade 2 or higher cytokine release syndrome or any grade immune effector cell-associated neurotoxicity syndrome after infusion, and high CAR T-cell expansion/persistence.

The researchers implemented multiple strategies to monitor and manage patients with movement and neurocognitive treatment-emergent adverse events across the ciltacabtagene autoleucel development program.

The strategies included enhanced bridging therapy to reduce the baseline tumor burden, early aggressive treatment of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and extended monitoring and reporting time for neurotoxicity beyond 100 days after a patient received the infusion.

After “successful implementation of these strategies” the incidence of movement and neurocognitive treatment-emergent adverse events was reduced from 5% to less than 1% across the ciltacabtagene autoleucel development program, “supporting its favorable benefit-risk profile” for multiple myeloma treatment, Dr. Cohen and colleagues wrote.

The investigators plan to continue the monitoring strategies and further study patient outcomes.

“Patients completing CARTITUDE-1 and other [ciltacabtagene autoleucel] clinical trials will be enrolled in a long-term follow-up study for continued monitoring for up to 15 years. A planned observational post-authorization safety study will focus on areas including characterization and evaluation of identified risks, and long-term safety,” Dr. Cohen and colleagues concluded. “Thus, the knowledge base about [ciltacabtagene autoleucel] treatment of [multiple myeloma] will continue to grow as data emerge on longer term efficacy and safety, mechanism of action, and patient perspectives.”

Reference

Cohen AD, Parekh S, Santomasso BD, et al. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J. 2022;12(2):32. doi:10.1038/s41408-022-00629-1