Earlier CAR-T: fewer cytopenias, bigger questions

In the issue of Blood Advances, Zeremski et al 1 reported a retrospective, real-world, multicenter analysis of hematologic toxicities in 82 patients, who received CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy as second-line (2L) treatment for relapsed or refractory large B-cell lymphoma.Using the standard European Hematology Association and the European Society for Blood and Marrow Transplantation consensus definition for neutropenic grading, N-ICAHT, 2 authors found lower incidence of severe early neutropenia (n = 10 12.2%) and multilineage cytopenia than previously reported in historical later-line cohorts.They also described an association between a high CAR-HEMATOTOX score at time of lymphodepletion (n = 14) with a more pronounced anemia and thrombocytopenia but not with severe N-ICAHT.Although clinical outcomes including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, progression-free survival (PFS), and overall survival (OS) rates were similar to those reported in 2L clinical trials, such as Zuma-7 3 and TRANSFORM, 4 they report that a high CAR-HEMATOTOX score may predict an inferior PFS but not OS.These observations provide an informative early picture of potential hematologic toxicities as CAR-T therapy moves into earlier lines of treatment.