Kesari, Vivek

AbstractBackgroundCD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has emerged as effective for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as immune effector cell–associated neurotoxicity syndrome (ICANS), is poorly understood. To better elucidate the clinical characteristics, treatment outcomes, and correlative biomarkers of ICANS, we review here a single-center analysis of ICANS after CAR T-cell therapy in R/R LBCL.MethodsPatients (n = 45) with R/R LBCL treated with axicabtagene ciloleucel (axi-cel) were identified. Data regarding treatment course, clinical outcomes, and correlative studies were collected. Patients were monitored and graded for ICANS via CARTOX-10 scoring and Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, respectively.ResultsTwenty-five (56%) patients developed ICANS, 18 (72%) of whom had severe (CTCAE grades 3–4) ICANS. Median time to development of ICANS was 5 days (range, 3–11). Elevated pre-infusion (day 0 [D0]) fibrinogen (517 vs 403 mg/dL, upper limit of normal [ULN] 438 mg/dL, P = 0.01) and D0 lactate dehydrogenase (618 vs 506 units/L, ULN 618 units/L, P = 0.04) were associated with ICANS. A larger drop in fibrinogen was associated with ICANS (393 vs 200, P < 0.01). Development of ICANS of any grade had no effect on complete remission (CR), progression-free survival (PFS), or overall survival (OS). Duration and total dose of steroid treatment administered for ICANS did not influence CR, PFS, or OS.ConclusionsICANS after CAR-T with axi-cel for R/R LBCL was seen in about half of patients, the majority of which were high grade. Contrary to previous reports, neither development of ICANS nor its treatment were associated with inferior CR, PFS, or OS. The novel finding of high D0 fibrinogen level can identify patients at higher risk for ICANS.

Background Ischemic stroke is a time-sensitive disease, with improved outcomes associated with decreased time from onset to treatment. It was hypothesised that ambulance-based assessment of the National Institutes of Health Stroke Scale (NIHSS) using a Health Insurance Portability and Accountability Act (HIPAA)–compliant mobile platform immediately prior to arrival is feasible. Methods This is a proof-of-concept feasibility pilot study in two phases. The first phase consisted of an ambulance-equipped HIPAA-compliant video platform for remote NIHSS assessment of a simulated stroke patient. The second phase consisted of remote NIHSS assessment by a hospital-based neurologist of acute stroke patients en route to our facility. Five ambulances were equipped with a 4G/LTE-enabled tablet preloaded with a secure HIPAA-compliant telemedicine application. Secondary outcomes assessed satisfaction of staff with the remote platform. Results Phase one was successful in the assessment of three out of three simulated patients. Phase two was successful in the assessment of 10 out of 11 (91%) cases. One video attempt was unsuccessful because local LTE was turned off on the device. The video signal was dropped transiently due to weather, which delayed NIHSS assessment in one case. Average NIHSS assessment time was 7.6 minutes (range 3–9.8 minutes). Neurologists rated 83% of encounters as ‘satisfied’ to ‘very satisfied’, and the emergency medical service (EMS) rated 90% of encounters as ‘satisfied’ to ‘very satisfied’. The one failed video attempt was associated with ‘poor’ EMS satisfaction. Conclusion This proof-of-concept pilot demonstrates that remote ambulance-based NIHSS assessment is feasible. This model could reduce door-to-needle times by conducting prehospital data collection.