CAR HEMATOTOX independently predicts outcomes after CD19 CAR-T therapy for acute lymphoblastic leukemia Open Access

• CAR HEMATOTOX identifies a subset of ALL CAR patients with low toxicity and excellent outcomes, independent of disease burden.

• In a smaller investigational cohort, HTlow patients had higher CAR expansion than HThigh patients for a given disease burden.

CAR-T treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as < 5% blasts in the bone marrow) is associated with better outcomes. CAR-HEMATOTOX (HT) is a score using pre-lymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the ROCCA consortium. An independent cohort of 61 ALL patients treated with an investigational CD19 CAR-T at one center was also described. Among 199 ROCCA patients, the 43 (22%) HTlow patients had lower rates of delayed neutrophil recovery than HThigh (26% vs. 52%, p = 0.002) and fewer severe infections (2.5% vs. 18.8%, p = 0.011). They had higher response rates, overall survival (OS) and event free survival (EFS), as well as lower non-relapse mortality and cumulative incidence of relapse (CIR). The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, HTlow patients had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes post CD19 CAR and higher CAR expansion in a single-center cohort. NCT01044069 and NCT01860937