Hypomagnesemia in lymphoma patients receiving CAR T therapy correlates with immune dysfunction and decreased survival

Figures

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  Fig. 1. Survival grouped by magnesium level. A Progression-free survival of patients with lymphoma in the ZUMA-1 cohort undergoing CAR-T by day -5 before the start of lymphodepleting chemotherapy serum magnesium level. p = 0.022. B Overall survival of patients with lymphoma in the ZUMA-1 cohort undergoing CAR-T by day -5 before the start of lymphodepleting chemotherapy serum magnesium level. p = 0.0013. (Low ≤ 1.7 mg/dL; Normal = 1.7 to < 2.0 mg/dL; High ≥2.0 mg/dL) C Progression-free survival of patients with lymphoma in the SOC cohort undergoing CAR-T by day -5 before the start of lymphodepleting chemotherapy serum magnesium level. p = 0.03. D Overall survival of patients with lymphoma in the SOC cohort undergoing CAR-T by day -5 before the start of lymphodepleting chemotherapy serum magnesium level. p = 0.13

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  Fig. 2. Correlation of magnesium level with inflammatory markers and monocyte transcriptome. A Magnesium level at the time of lymphodepletion chemotherapy (Mg at LD Chemo) and ferritin at LD chemo, CART infusion, and CART peak levels (column labels) are shown for ZUMA-1 study (top row) and Mayo SOC cohort (bottom row). B Mg level prior to CART (x-axis) and cytokine IL1RAare shown for time points as labeled for each column for ZUMA-1 study. (A and B Lines represent linear regression. The shaded region represents a 95% confidence interval. Pearson correlation and p-value are noted in the graph.) C GSEA analysis for enriched pathways is shown for CD14 + monocytes and CD16 + monocytes, comparing patients with MgHigh (Mg ≥ 2.0 mg/dL) and with Mglow (Mg < 2.0 mg/dL)

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  Fig. 3. Cytokine release syndrome and neurotoxicities by magnesium level. Magnesium levels for patients in the ZUMA-1 study at the time of lymphodepletion chemotherapy (Mg at LD) are shown for patients experiencing grade 3 or higher cytokine release syndrome (CRS) (A) and neurotoxicity (B). ASTCT guideline was used for CRS and neurologic events grading in the SOC cohorts

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  Fig. 4. Immune cell interactions by magnesium levels. Heatmap showing the differential number of interactions (A) and strength of interactions (B) among the indicated immune cells at CAR-T infusion and at CAR-T peak (C, D)

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  Fig. 5. Transcription factor analysis by magnesium levels. Transcription factor analysis identifying the factors significantly expressed at CART-Peak in patients with Mghigh (A) and those with Mglow (B)