Mathematical modeling unveils the timeline of CAR-T cell therapy and macrophage-mediated cytokine release syndrome
Fig 5
Patient-specific pharmacological and clinical parameters evaluated from model fits. A–D Within the patient level, the fold change in IL-6 concentration (baseline to peak) cannot be predicted from a single indicator, such as total CAR-T dose, initial tumor burden, CAR-T cell fold change (dose to peak), or time of IL-6 peak. E However, for the majority of patients, the model predicts that the peak of CAR-T cells occurs between 0 and 5 days after the cytokine peak (gray area). F For all patients, the cytokine peak is predicted to occur between 0 and 2 days after the peak of activated macrophages (gray area). G,H The tumor burden at days 28 and 90 post-therapy initiation shows a weak negative correlation with CAR-T cell fold change (a value of 0.1 cells is assigned for cases where the model predicts zero tumor cells). I The model predicts a moderate correlation between tumor burden responses at days 28 and 90. In each panel, the best linear fit for the red points is shown in light red, and the corresponding correlation coefficient and p-value are given.