Several clinical and radiologic features were associated with neurotoxicity, or immune effector cell-associated neurotoxicity syndrome (ICANS), among patients with large B-cell lymphoma (LBCL) who received axicabtagene ciloleucel (axi-cel), including ferritin and C-reactive protein (CRP) levels, monocyte count, magnetic resonance imaging (MRI) patterns, and electroencephalographic (EEG) abnormalities, according to a cohort study published in Blood Advances.1
Although ICANS is a common adverse event (AE) associated with the administration of chimeric antigen receptor (CAR) T-cell (CAR-T) therapy — affecting approximately two-thirds of patients — “there is very limited information available on the radiologic and electroencephalographic (EEG) features associated with ICANS in patients with LBCL treated with axi-cel,” the authors wrote.
The cohort study included 100 consecutive patients with relapsed or refractory LBCL treated with axi-cel outside of clinical trials at The University of Texas MD Anderson Cancer Center, Houston, between January 2018 and May 2019. All patients received lymphodepleting chemotherapy and antiseizure prophylaxis with levetiracetam.
The median patient age was 60 years, and the median number of prior lines of treatment was 4 (range, 2-15). Cytokine release syndrome (CRS) developed in 97% of patients, with 9% experiencing grade 3 or higher CRS.
Any-grade ICANS developed in 68% of patients, with 41% experiencing grade 3 or higher, with a median time to onset of 5 days (range, 0-25 days). The duration was a median of 6 days (range, 0-52 days) and no new cases of ICANS developed after 30 days.
There was no association between preconditioning laboratory values and high-grade ICANS. However, 30-day peak ferritin (P =.03) and CRP (P =.001) were significantly associated with grade 3 or higher ICANS compared with grade 0 to 2 ICANS. Lower median absolute monocyte count (P =.001) was also associated with grade 3 or above ICANS. There was no association between ICANS and median peak absolute lymphocyte count.
Among the 38 patients who developed ICANS and underwent both MRI and preconditioning at the time of ICANS symptoms, 14 showed positive findings with 4 common patterns, including encephalitis, stroke, leptomeningeal disease, and posterior reversible encephalopathy syndrome.
There were 50 abnormal findings among the 55 patients with ICANS who underwent EEG, with the most common abnormality of diffuse slowing. Other abnormalities, which occurred less commonly, were intermittent interictal epileptiform discharges and nonconvulsive status epilepticus.
Shorter survival was associated with high-grade ICANS. The 6-month progression-free survival was 40% among patients with grade 3 or higher ICANS compared with 60% among patients with grade 0 to grade 2 ICANS (P =.02). Similarly, the 6-month overall survival was 50% and 78% among patients with grade 3 or higher and grade 0 to grade 2 ICANS, respectively (P =.001).
“This is an interesting finding, because all ICANS events (except for 1) were reversible, suggesting that their effect on survival was not direct,” the authors wrote.
The authors concluded: “Imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.”
Disclosure: Some of the authors disclosed financial relationships with pharmaceutical companies. For a full list of disclosures, please refer to the original study.
Strati P, Nastoupil LJ, Westin J, et al. Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020;4(16):3943-3951. doi:10.1182/bloodadvances.2020002228