Infections in Patients With Cytokine Release Syndrome/Immune Effector Cell–Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T-Cell Therapy

Figures

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  Figure 1.. Vital signs and laboratory parameters at cytokine release syndrome (CRS)/immune effector cell–associated neurotoxicity syndrome (ICANS) onset and at infection diagnosis, with infection cases stratified by multimodal immunosuppression. Infectious episodes were stratified according to receipt of multimodal immunomodulatory therapy (≥2 doses of tocilizumab plus high-dose corticosteroids vs none). Vital signs and laboratory parameters were recorded at CRS/ICANS onset and at the time of infection diagnosis. Vital signs: heart rate (HR; beats/min), respiratory rate (RR; breaths/min), systolic blood pressure (SBP; mmHg), temperature (axillary) (Temp(ax); °C), and peripheral oxygen saturation (SpO2; %). Laboratory parameters: C-reactive protein (CRP; mg/L), lymphocyte count (×109/L), and neutrophil count (×109/L). Outliers were excluded from visualization using the 1.5× interquartile range (IQR) rule; all data were included in statistical testing (Wilcoxon rank-sum test).

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  Figure 2.. Bacterial, viral, and fungal infections according to immunomodulatory therapy and underlying hematological disease in chimeric antigen receptor (CAR) T-cell therapy episodes with cytokine release syndrome (CRS) and/or immune effector cell–associated neurotoxicity syndrome (ICANS). (A) Comparison of the proportion of episodes with bacterial, viral, and fungal infections between episodes with and without immunomodulatory therapy (darker vs lighter bars, respectively). (B and C) The distribution of infections stratified by underlying hematological disease among episodes with immunomodulatory therapy (B) and without immunomodulatory therapy (C). P-values were calculated using Fisher's exact test. Abbreviations: ALL, acute lymphoblastic leukemia; MM, multiple myeloma; NHL, non-Hodgkin lymphoma.

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  Figure 3.. Infections and clinical events in patients with CRS and/or ICANS requiring immunomodulatory therapy after CAR-T infusion: (A) CRS with concomitant ICANS (n = 18), (B) CRS grades 2–4 without ICANS (n = 22), and (C) CRS grade 1 without ICANS (n = 30). Each horizontal lane represents 1 patient (sex, age, and hematologic disease on the left). Time is anchored at day 0 (first infusion, A1). Circles indicate aliquot collections (A1–A3; in cesnicabtagene autoleucel, A4 is omitted). Upward triangles denote administration of tocilizumab or anakinra . Horizontal bars indicate systemic corticosteroids (high dose or standard dose). Circles indicate infections categorized by etiology (bacterial, viral, or fungal) and annotated above the timeline. Abbreviations: ALL, acute lymphoblastic leukemia; BSI, bloodstream infection; CDI, Clostridioides difficile infection; CMV, cytomegalovirus; CNS, central nervous system; CR, carbapenem-resistant; CRBSI, catheter-related bloodstream infection; CRS, cytokine release syndrome; DTR, difficult-to-treat; HHV-6, human herpesvirus 6; HSV-1, herpes simplex virus 1; ICANS, immune effector cell–associated neurotoxicity syndrome; IPA, invasive pulmonary…

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  Figure 4.. Cumulative incidence of the first microbiologically documented infection by multimodal immunosuppression status. Numbers at risk represent patients remaining under observation at each time point, stratified according to multimodal immunosuppression status. Follow-up was administratively censored at day 60. Abbreviations: A1, aliquot 1; CAR-T, chimeric antigen receptor T-cell.

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  Figure 5.. Forest plot of univariable and multivariable Fine–Gray competing-risk analyses for factors associated with the first infection, with death as a competing event. Subdistribution hazard ratios (sHRs), 95% CIs, and P-values are presented. Abbreviations: BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T-cell; CRS, cytokine release syndrome; HSCT, hematopoietic stem cell transplant; ICANS, immune effector cell–associated neurotoxicity syndrome; sHR, subdistribution hazard ratio.