CRP and ferritin in addition to the EASIX score predict CAR-T-related toxicity

Uri Greenbaum, Paolo Strati, Rima M. Saliba, Janet Torres, Gabriela Rondon, Yago Nieto, Chitra Hosing, Samer A. Srour, Jason Westin, Luis E. Fayad, Hun J. Lee, Swaminathan P. Iyer, Ranjit Nair, Loretta J. Nastoupil, Simrit Parmar, Maria A. Rodriguez, Felipe Samaniego, Raphael E. Steiner, Michael Wang, Chelsea C. PinnixChristopher R. Flowers, Sudhakar Tummala, Jeremy L. Ramdial, Fevzi F. Yalniz, Misha Hawkins, Katayoun Rezvani, Richard E. Champlin, Elizabeth J. Shpall, Sattva S. Neelapu, Partow Kebriaei, Sairah Ahmed

    Research output: Contribution to journalArticlepeer-review

    66 Scopus citations

    Abstract

    The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine 3 lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P 5 .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P 5 .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.

    Original languageEnglish
    Pages (from-to)2799-2806
    Number of pages8
    JournalBlood advances
    Volume5
    Issue number14
    DOIs
    StatePublished - 27 Jul 2021

    ASJC Scopus subject areas

    • Hematology

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