GM-CSF neutralization in vivo ameliorates CRS after CART19 therapy in a xenograft model. (A) Lenzilumab and anti-mouse GM-CSF antibody prevent CRS-induced weight loss compared with mice treated with CART19 cells and isotype-control antibodies; 3 mice per group, 2-way analysis of variance. Data are mean ± SEM. (B) Human GM-CSF was neutralized in patient-derived xenografts treated with lenzilumab and mouse GM-CSF–neutralizing antibody; 3 mice per group. Data are mean ± SEM. *P < .05, ***P < .001, Student t test. (C) Human cytokine/chemokine heat map (serum collected 11 days after CART19 cell injection) exhibits increases in cytokines and chemokines typical of CRS after CART19 cell treatment. GM-CSF neutralization results in a significant decrease in several cytokines and chemokines compared with mice treated with CART19 cells and isotype-control antibodies, including several myeloid-associated cytokines and chemokines, as indicated in the panel; 3 mice per group, serum from day 11 post–CART19 cell injection. *P < .05, **P < .01, ***P < .001, GM-CSF neutralizing antibody–treated mice vs isotype control–treated mice that received CAR-T cell therapy, Student t test. (D) Mouse cytokine/chemokine heat map (serum collected 11 days after CART19 cell injection) exhibits increases in mouse cytokines and chemokines typical of CRS after CART19 cell treatment. GM-CSF neutralization results in a significant decrease in several cytokines and chemokines compared with treatment with CART19 cells with control antibodies, including several myeloid-differentiating cytokines and chemokines, as indicated in the panel; 3 mice per group, serum from day 11 post–CART19 cell injection, *P < .05, GM-CSF neutralizing antibody–treated mice vs isotype control–treated mice that received CAR-T cell therapy, Student t test.