Toxicity in CAR-37 patients correlates with increased serum cytokines. (A) The timing, grade, and duration of CRS (open bars) and ICANS (dotted bars) after CAR-37 T-cell infusion (day 0) are shown. The bar color indicates grade, as noted. Open/white bars indicate duration with no CRS or ICANS symptoms. (B) As part of the diagnostic workup for CRS and ICANS, ferritin (left y-axis, closed symbols) and c-reactive protein (CRP; right y-axis, open symbols) were measured in patient serum over time. The solid black line indicates the maximum normal ferritin level. The dashed black line indicates the maximum normal CRP level. The underlaying horizontal bars indicate the timing and duration of treatment for CRS or ICANS, as noted by the treatment name in the bar. Bars in the same row represent the same treatment. (C) Cell counts per microliter of blood pre- and post-CAR-37 infusion (day 0). Dashed lines indicate the normal range for each cell type. (D) Hematoxylin and eosin staining (20× original magnification) of bone marrow biopsies taken from patients 4 and 5 on day 27 after CAR-37 T-cell infusion. ANC, absolute neutrophil count; G-CSF, granulocyte colony-stimulating factor; Sil, siltuximab; Toci, tocilizumab; WBC, white blood cell.
Figure 3.

Toxicity in CAR-37 patients correlates with increased serum cytokines. (A) The timing, grade, and duration of CRS (open bars) and ICANS (dotted bars) after CAR-37 T-cell infusion (day 0) are shown. The bar color indicates grade, as noted. Open/white bars indicate duration with no CRS or ICANS symptoms. (B) As part of the diagnostic workup for CRS and ICANS, ferritin (left y-axis, closed symbols) and c-reactive protein (CRP; right y-axis, open symbols) were measured in patient serum over time. The solid black line indicates the maximum normal ferritin level. The dashed black line indicates the maximum normal CRP level. The underlaying horizontal bars indicate the timing and duration of treatment for CRS or ICANS, as noted by the treatment name in the bar. Bars in the same row represent the same treatment. (C) Cell counts per microliter of blood pre- and post-CAR-37 infusion (day 0). Dashed lines indicate the normal range for each cell type. (D) Hematoxylin and eosin staining (20× original magnification) of bone marrow biopsies taken from patients 4 and 5 on day 27 after CAR-37 T-cell infusion. ANC, absolute neutrophil count; G-CSF, granulocyte colony-stimulating factor; Sil, siltuximab; Toci, tocilizumab; WBC, white blood cell.

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