Using a clock drawing task as an adjunct screening tool could speed up detection of immune effector cell-associated neurotoxicity syndrome (ICANS) in patients receiving CAR T therapy for blood cancers, an Australian study suggests.

A multidisciplinary team from Monash University and Alfred Health in Melbourne said the immune effector cell-associated encephalopathy (ICE) score was currently used to define ICANS, however more mild or subtle symptoms of brain toxicity could elude this “crude” measurement and potentially delay diagnosis.

Their study demonstrated that when a clock drawing task – already used to assess cognitive decline in conditions like dementia, multiple sclerosis, traumatic brain injury and stroke – was used in conjunction with the traditional ICE score small neurological changes were picked up earlier.

The short two-minute test which is as the name suggests can be administered routinely by clinical staff including nurses and doctors.

“It’s a simple tool that captures executive dysfunction and visuospatial deficits often missed by conventional assessments,” said study lead investigator Christina Kazzi, a neuroscience PhD student and clinical neuropsychologist.

The study involved a total of 1208 clock drawings time matched within an hour of an ICE score for 54 patients (39% female, mean age 64), of whom 26% developed ICANS.

Findings published in the British Journal of Haematology [link here] demonstrated a significant correlation between changes in modified CLOX (executive clock drawing task) scores and ICE scores, with the clock drawing task offering high specificity for identifying ICANS-related cognitive decline.

A drop of two or more points in the modified CLOX score was strongly predictive of ICANS onset, even when the ICE score indicated normal brain functioning.

“The CLOX-­M score demonstrated excellent specificity, low sensitivity, high positive and predictive values, high positive likelihood ratio and weak negative likelihood ratio. Clinicians can be confident that a positive test result (patient scores ≤−2 on CLOX-­M) confirms the presence of ICANS,” the researchers said.

“While a negative test result (patient scores >−2 on CLOX-­ M) suggests that the patient may not have ICANS, further assessment is needed. Hence, we suggest that there is a rationale for utilising both the CDT and ICE score.”

They added: “Changes in CLOX-­ M score, when the ICE score remains 10 [indicating normal brain functioning], can prompt more frequent bedside assessments and observations to more readily capture a rapidly evolving ICANS.

“In cases when there is a mild ICE score change (e.g. 7–9/10) accompanied by an abnormal clock, clinicians may consider initiating glucocorticoids for Grade 1 ICANS over more conservative management and/or waiting for higher grade ICANS to initiate treatment.”

The team are also investigating blood and imaging biomarkers, and CAR T-cell expansion dynamics, with the hope of significantly improving diagnosis and management of CART related neurotoxicity when used in combination.

Study senior author Associate Professor Mastura Monif said: “CAR T therapy is novel and assessments of neurotoxicity need to be optimised to detect the toxicity early, to characterise it better and to institute treatment as soon as feasible. Ultimately detecting neurotoxicity sooner can improve patient outcomes, and that is where our work focuses on.”