T-ICAHT: Grading and Prognostic Impact of Thrombocytopenia After CAR T-cell Therapy

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.

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Journal
Blood
Published
2025-04-21
DOI
https://doi.org/10.1182/blood.2025028833
Citations
20
Primary Topic
CAR-T cell therapy research
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article
Field-Weighted Citation Impact
20.91
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T-ICAHT: Grading and Prognostic Impact of Thrombocytopenia After CAR T-cell Therapy

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T-ICAHT: Grading and Prognostic Impact of Thrombocytopenia After CAR T-cell Therapy

Hamza Hashmi, Saad Z. Usmani, Tsila Zuckerman, Marina Gómez-Llobell, Avichai Shimoni, Ronit Marcus, Frederick Lundry Locke, Gunjan L. Shah, Monica Nair, Marcela V. Maus, Nirali N. Shah, Roni Shouval, Ofrat Beyar‐Katz, Jaime Sanz, Veit Bücklein, Netta Glaubach, Michael Scordo, Maria Lia Palomba, Kai Rejeski, Kevin J. Curran, Abraham Avigdor, Jonathan H. Esensten, Sandeep S. Raj, Sham Mailankody, Sridevi Rajeeve, Orit Itzhaki, Sigrun Einarsdottir, Miguel‐Angel Perales, Gilles Salles, Marcelo C. Pasquini, Yannis K. Valtis, Tobias Tix, Teng Fei, Jae H. Park, Noa Golan-Accav, Iris Halamis, Ori Ben Valid
article en
20 citations

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.

BloodVol. 146(7)
National Institutes of Health (US), Memorial Sloan Kettering Cancer Center (US), Harvard University (US), Tel Aviv University (IL), Medical College of Wisconsin (US), Sheba Medical Center (IL), Rambam Health Care Campus (IL), LMU Klinikum (DE), Hospital Universitari i Politècnic La Fe (ES), Moffitt Cancer Center (US), Massachusetts General Hospital (US), National Cancer Institute (US), Center for Cancer Research (US), Ludwig-Maximilians-Universität München (DE)
Openalex Percentile: Top 0%
CAR-T cell therapy research
20.91
DOIOpen Access PDFOpenAlex
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