Applying the EHA/EBMT Grading for ICAHT after CAR-T: Comparative Incidence and Association with Infections and Mortality.

Cytopenias represent the most common side effect of CAR T-cell therapy and can predispose for severe infectious complications. Current grading systems such as the CTCAE neither reflect the unique quality of post CAR-T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia. For this reason, a novel EHA/EBMT consensus grading was recently developed for Immune Effector Cell-Associated HematoToxicity (ICAHT). In this multicenter observational study, we applied the grading system to a large real-world cohort of 549 patients treated with BCMA- or CD19 CAR-T for refractory B-cell malignancies (112 MM, 334 LBCL, 103 MCL) and examined the clinical sequelae of severe (≥3°) ICAHT. The ICAHT grading was strongly associated with the cumulative duration of severe neutropenia (r=0.92, p<0.0001), presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. We noted an increased rate of severe ICAHT in MCL vs. LBCL and MM patients (28% vs. 23% vs. 15%). Severe ICAHT was associated with a higher rate of severe infections (49% vs. 13%, p<0.0001), increased NRM (14% vs. 4%, p<0.0001), and inferior survival outcomes (1-year PFS 35% vs. 51%, 1-year OS 52% vs. 73%, both p<0.0001). Importantly, the ICAHT grading demonstrated superior capacity to predict severe infections compared to CTCAE grading (c-index 0.73 vs. 0.55, p<0.0001 vs. non-signficant). Taken together, these data highlight the clinical relevance of the novel grading system and support the reporting of ICAHT severity in clinical trials evaluating CAR-T therapies.

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