ALL-Hematotox score: Predicting post-CAR T-cell therapy hematotoxicity in B-cell ALL

Immune effector cell-associated hematotoxicity (ICAHT) is a major B cell-targeted CAR T-cell therapy-related complication.¹ Although the incidence and severity of ICAHT have been documented in LBCL, MCL, and MM, they remain to be described in B-ALL. The CAR-Hematotox (CAR-HT) model, designed to predict severe prolonged neutropenia (≥14 days of ANC <500/μL), also remains to be validated in B-ALL.¹ 

Nair et al.¹ conducted a retrospective analysis (NCT03827343) of data from children, adolescents, and young adults with R/R B-ALL treated with CAR T-cell therapies in phase I clinical trials targeting CD19 and/or CD22 at the NIH NCI between July 2012 and June 2023 (n = 156) in order to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. 

The primary objectives were to apply early ICAHT grading and assess the applicability of CAR-HT in B-ALL for predicting severe prolonged neutropenia, from CAR T-cell therapy infusion (Day 0 [D0]) until Day +30 (D30).¹ They then aimed to refine the model for its use in B-ALL. Their findings were published in Blood.¹

Key learnings

The median age of patients was 16 years (4–39 years) and 69% were male. There was a high incidence of early ICAHT, with a median duration of severe neutropenia (ANC <500/μL) of 13 days (95% CI, 10–16 days), and 53% of patients experiencing Grade ≥3 ICAHT.

Applying CAR-HT, 87% of patients were classified as high-risk, demonstrating limited discriminative power in B-ALL. The ALL-HT score was developed as a B-ALL-specific optimized CAR-HT model by replacing ferritin with BM disease burden. 

The ALL-HT score was associated with severe prolonged neutropenia and discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 days vs 4 days; p < 0.0001), fewer rates of CR (88% vs 98%; p = 0.03), and shorter median OS (9.8 months vs 24 months; log-rank p = 0.0002).

The ALL-HT score refines a widely accepted predictive model of post CAR T-cell therapy cytopenias, optimizing applicability to B-ALL by incorporating BM disease involvement. Further application, validation, and assessment for associations with other clinical outcomes (e.g., infection, hospitalization duration, and PFS) are important next steps.