Autonomic dysfunction as manifestation of ICANS: A case report

Abstract

Rationale: Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a successful treatment for B-cell malignancies associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cardiovascular toxicities have also been reported in this setting. However, there is scarce data regarding development of autonomic disorders after CAR-T cell therapy.

Patient concerns: We report a case with a patient with non-Hodgkin B-cell lymphoma, refractory to 2 prior lines of immunochemotherapy, treated with CAR-T therapy.

Diagnoses: Orthostatic hypotension secondary to autonomic dysfunction was diagnosed as manifestation of ICANS.

Interventions: The patient received metilprednisolone 1000 mg IV daily for 3 days and anakinra 100 mg IV every 6h.

Outcomes: The vast majority of autonomic symptoms ceased and 4 months after CAR-T therapy, autonomic dysfunction was resolved.

Lessons: New-onset autonomic dysfunction can occur as manifestation of ICANS in patients who experience persistent neurologic and cardiovascular symptoms after resolution of acute neurotoxicity and should be early recognized. Differences in differential diagnosis, mechanisms and treatment approaches are discussed.

Figure 1.

(A) Anterior-posterior bipolar montage and referential montage EEG with intermittent bursts of bilateral frontal intermittent rhythmic delta activity (FIRDA) over an underlying mild diffuse slowing of background activity; (B) FLAIR-T2 weighted axial view and T1-weighted dynamic contrast-enhanced coronal view brain MRI with normal results. EEG = electroencephalogram, MRI = magnetic resonance imaging.

Figure 2.

Graphic evolution of blood pressure and heart rate measurements. X-axis - days after CAR-T therapy infusion; Y-axis—blood pressure measured in mm Hg; blue represents blood pressure measured in supine position; green represents blood pressure measured in a seated position; orange represents blood pressure measured in supine position; red represents heart rate during measurements in bpm.

Figure 3.

(A) R-R Interval Analysis. Basal heart rate (73 bpm) increases after 5 min of breathing at 6 cycles per minute (79 bpm). (B) Sympathetic skin response with normal results.

Figure 4.

Graphic with evolution of peripheral blood (PB) CAR-T cells by flow cytometry: X axis—days after CAR-T therapy infusion (+1, +7, +14, +21, +28, +60, +90, and + 120 d); Y axis—number of CAR-T CD19 cells in PB by flow cytometry in %.