T-ICAHT: Grading and prognostic impact of thrombocytopenia after CAR T-cell therapy Journal Article
| Authors: | Rejeski, K.; Sanz, J.; Fei, T.; Nair, M. S.; Hashmi, H.; Avigdor, A.; Beyar-Katz, O.; Bücklein, V. L.; Curran, K. J.; Einarsdottir, S.; Esensten, J. H.; Glaubach, N.; Golan-Accav, N.; Gomez-Llobell, M.; Halamis, I.; Itzhaki, O.; Locke, F. L.; Mailankody, S.; Marcus, R.; Maus, M. V.; Palomba, M. L.; Park, J. H.; Pasquini, M.; Raj, S.; Rajeeve, S.; Salles, G.; Scordo, M.; Shah, G. L.; Shimoni, A.; Subklewe, M.; Tix, T.; Usmani, S. Z.; Valid, O.; Valtis, Y. K.; Zuckerman, T.; Shah, N. N.; Perales, M. A.; Shouval, R. |
| Article Title: | T-ICAHT: Grading and prognostic impact of thrombocytopenia after CAR T-cell therapy |
| Abstract: | Immune effector cell–associated hematotoxicity (ICAHT) was recently introduced as a distinct toxicity category of chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. Although a grading system based solely on neutrophil counts was proposed (hereafter termed N-ICAHT), the prevalence and prognostic impact of thrombocytopenia remain poorly defined. In this multicenter observational study, we systematically examined patterns of thrombocytopenia in 744 patients treated with commercial CD19 CAR-T for B-cell non-Hodgkin lymphoma (B-NHL). We developed a grading system termed T-ICAHT, with thresholds that closely aligned with N-ICAHT, based on depth, duration, and timing of thrombocytopenia. In the core NHL data set, 43% of patients developed any-grade early T-ICAHT (days 0-30), with 23% developing severe (grade ≥3) manifestations. Late T-ICAHT (days 31-100) was observed in 42% (grade ≥3, 13%). Although T-ICAHT and N-ICAHT gradings showed some correlation, considerable discordance was noted. On multivariate analysis, bridging therapy, poor performance status, and high HEMATOTOX scores were associated with increased risk of severe early T-ICAHT. Patients with higher T-ICAHT grades showed increased platelet and red blood cell transfusion burden and more bleeding events. T-ICAHT grades were inversely associated with overall survival (OS), with landmarked 2-year estimates ranging from 67% (grade 0) to 48% (grade 1-2) and 35% (grade ≥3). In multivariable Cox regression analysis, the independent prognostic capacity of T-ICAHT for OS was confirmed. Finally, we validated T-ICAHT's clinical and prognostic utility in 3 external cohorts spanning an additional 599 pediatric and adult patients (NHL, multiple myeloma, and B-cell acute lymphoblastic leukemia), confirming its broad applicability. These findings support integrating T-ICAHT into the ICAHT framework to standardize thrombocytopenia grading in CAR-T recipients. © 2025 American Society of Hematology |
| Journal Title: | Blood |
| Volume: | 146 |
| Issue: | 7 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Publication status: | Published |
| Date Published: | 2025-08-14 |
| Start Page: | 834 |
| End Page: | 846 |
| Language: | English |
| DOI: | 10.1182/blood.2025028833 |
| PUBMED: | 40258181 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Roni Shouval -- Source: Scopus |
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