Table 2.

Summary of select abstracts presented at the 2021 Annual Meetings of the American Society of Clinical Oncology and the American Society of Hematology

First Author	Title	Study Aim	Study design	Population	Sample Size	CAR-T target and product	Outcome(s)
Clinical manifestations of Immune effector cell-associated neurotoxicity syndrome (ICANS)
Einslee et al.42	Incidence, mitigation, and management of neurologic adverse events in patients with multiple myeloma (MM) treated with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-2	To describe the clinical features and management of ICANS	Phase II open label	Relapsed multiple myeloma	n=20	BCMA: Cilta-cel (JNJ-68284528)	ICANS developed in n=4 (20%); median time to onset of symptoms: 8 days (range: 7–11), median duration of ICANS: 2 days (range: 1–2). Management of ICANS included: levetiracetam and steroids; all 3 patients with ICANS had concurrent cytokine release syndrome (CRS) and all recovered. One patient developed isolated facial paralysis on Day 29 post infusion, that resolved 51 days post onset of symptoms and with dexamethasone therapy.
Biomarkers and predictors of ICANS development
Gauthier et al.43	CD19 CAR T-cell product type independently impacts CRS and ICANS severity in patients with aggressive NHL	To assess the impact of 3 CD19 CAR T-cell products (axicabtagene ciloleucel, tisagenlecleucel, and JCAR014) on CRS and ICANS severity	retrospective	Relapsed, refractory Non-Hodgkin’s lymphoma	n=136	CD19: Axicabtagene ciloleucel, Tisagenlecleucel BCMA: JCAR014	Factors associated with ICANS severity CAR T-cell product type (Tisagenlecleucel vs axicabatagene ciloleucel OR = 0.14, p <.001; JCAR014 vs axicabatagene ciloleucel, OR = 0.31, p = 0.009) Pre-lymphodepletion LDH (OR, 3.96 per log10 increase; p = 0.04) Age (OR per 10-year increase, 1.32; p =.06)
Butt et al.44	Pre-Infusion Neurofilament Light Chain (NfL) Levels Predict the Development of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) - a Multicenter Retrospective Study	To evaluate pre-infusion levels of plasma neurofilament light chain (NfL), a marker of neurodegeneration, as a predictive biomarker of ICANS	retrospective	not reported	not reported	not reported	n=30 (36%) with ASTCT Gr 1–4 ICANS, higher NfL were found in those who developed ICANS compared to those who did not ([87.6 v 29.4 pg/ml], p = 0.00004); NfL correlated with ICANS development (r = 0.74, p < 0.0001)
Korell et al.45	Easix Predicts Severe Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neuro-Toxicity Syndrome (ICANS) in Patients Receiving CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy	To evaluate and validate the Endothelial Activation and Stress Index (EASIX)) as a predictor for CRS and ICANS in patients receiving CD19-directed CAR-T cells	retrospective	Relapsed, refractory large B-cell lymphoma Acute lymphoblastic leukemia Mantle cell lymphoma Chronic lymphocytic leukemia Follicular lymphoma	n=107 (training cohort) n=93 (validation cohort)	CD19: Axicabtagene ciloleucel, Tisagenlecleucel	n=24 patients (22%) developed ICANS grades 1–4. Grade ≥ 3 ICANS occurred in 11 patients (11%; median onset 8 (4–17) days). EASIX values (pre-lymphodepletion, d0, d3, d7) were significantly higher in patients who developed either grade 3–4 CRS, ICANS, or both; EASIX predicted grade 3–4 CRS and ICANS before lymphodepleting therapy (-pre), on day 0 and on day 3 in both cohorts
Management of ICANS
Gazeau et al.41	Safety and Efficacy of Two Anakinra Dose Regimens for Refractory CRS or ICANS after CAR T-Cell Therapy	To describe the safety and efficacy of two anakinra dose regimens to treat refractory CRS and/or ICANS after CAR T-cell therapy	retrospective	Multiple myeloma Mantle cell lymphoma Transformed follicular lymphoma Diffuse large B-cell lymphoma Steroid-refractory ICANS	n=26	not reported	Intervention: Anakinra 100–200mg/day subcutaneously (SC) in 13 patients (pts) or 8mg/kg/day SC or intravenously (IV) in 13 patients. Treatment with anakinra led to improved ICANS/CRS rates in 73% of patients with higher response in those who received the higher dose of anakinra
Frigault et al.40	A Phase II Trial of Anakinra for the Prevention of CAR-T Cell Mediated Neurotoxic	To evaluate whether or not anakinra could be administered prophylactically to prevent severe CRS and neurologic events (NE) in patients receiving axicabtagene ciloleucel	Phase II, open-labelled	Relapsed/refractory large cell lymphoma	N=6	CD19: Axicabtagene ciloleucel	Intervention: Anakinra 200 mg SC starting 4 hours prior to axicabatagene ciloleucel infusion and daily thereafter for a total of 7 days. 2 of 6 patients experienced grade 3 ICANS