Development and validation of predictive models of early immune effector cell–associated hematotoxicity
Abstract: Immune effector cell–associated hematotoxicity (ICAHT) is associated with morbidity and mortality after chimeric antigen receptor (CAR) T-cell therapy. To date, the factors associated with ICAHT are poorly characterized, and there is no validated predictive model of ICAHT as defined by cur...
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Elsevier
2025-02-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924006876 |
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| author | Emily C. Liang Jennifer J. Huang Andrew J. Portuguese Valentín Ortiz-Maldonado Aya Albittar Natalie Wuliji Ryan Basom Yein Jeon Qian Wu Aiko Torkelson Delaney Kirchmeier Abigail Chutnik Barbara Pender Mohamed Sorror Joshua A. Hill Noam E. Kopmar Rahul Banerjee Andrew J. Cowan Damian Green Ajay K. Gopal Christina Poh Mazyar Shadman Alexandre V. Hirayama Brian G. Till Erik L. Kimble Lorenzo Iovino Aude G. Chapuis Folashade Otegbeye Ryan D. Cassaday Filippo Milano Cameron J. Turtle David G. Maloney Jordan Gauthier |
| author_facet | Emily C. Liang Jennifer J. Huang Andrew J. Portuguese Valentín Ortiz-Maldonado Aya Albittar Natalie Wuliji Ryan Basom Yein Jeon Qian Wu Aiko Torkelson Delaney Kirchmeier Abigail Chutnik Barbara Pender Mohamed Sorror Joshua A. Hill Noam E. Kopmar Rahul Banerjee Andrew J. Cowan Damian Green Ajay K. Gopal Christina Poh Mazyar Shadman Alexandre V. Hirayama Brian G. Till Erik L. Kimble Lorenzo Iovino Aude G. Chapuis Folashade Otegbeye Ryan D. Cassaday Filippo Milano Cameron J. Turtle David G. Maloney Jordan Gauthier |
| author_sort | Emily C. Liang |
| collection | DOAJ |
| description | Abstract: Immune effector cell–associated hematotoxicity (ICAHT) is associated with morbidity and mortality after chimeric antigen receptor (CAR) T-cell therapy. To date, the factors associated with ICAHT are poorly characterized, and there is no validated predictive model of ICAHT as defined by current consensus criteria. Therefore, we performed comprehensive univariate analyses to identify factors associated with severe (grade 3-4) early ICAHT (eICAHT) in 691 patients who received commercial or investigational CAR T-cell therapy for hematologic malignancies. In univariate logistic regression, preinfusion factors associated with severe eICAHT included disease type (acute lymphoblastic leukemia), prelymphodepletion (pre-LD) blood counts including absolute neutrophil count (ANC), lactate dehydrogenase (LDH), and inflammatory (C-reactive protein [CRP], ferritin, and interleukin-6 [IL-6]) and coagulopathy biomarkers (D-dimer). Postinfusion laboratory markers associated with severe eICAHT included early and peak levels of inflammatory biomarkers (CRP, ferritin, and IL-6), coagulopathy biomarkers (D-dimer), peak cytokine release syndrome grade, and peak neurotoxicity grade. We trained (n = 483) and validated (n = 208) 2 eICAHT prediction models (eIPMs): eIPMPre including preinfusion factors only (disease type and pre-LD ANC, platelet count, LDH, and ferritin) and eIPMPost containing both preinfusion (disease type and pre-LD ANC, platelet count, and LDH) and early postinfusion (day +3 ferritin) factors. Both models generated calibrated predictions and high discrimination (area under the receiver operating characteristic curve in test set, 0.87 for eIPMPre and 0.88 for eIPMPost), with higher net benefit in decision curve analysis for eIPMPost. Individualized predictions of severe eICAHT can be generated from both eIPMs using our online tool (available at https://eipm.fredhutch.org). |
| format | Article |
| id | doaj-art-50fba9dd0b8e42d4890545f464640559 |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-50fba9dd0b8e42d4890545f4646405592025-02-05T04:32:27ZengElsevierBlood Advances2473-95292025-02-0193606616Development and validation of predictive models of early immune effector cell–associated hematotoxicityEmily C. Liang0Jennifer J. Huang1Andrew J. Portuguese2Valentín Ortiz-Maldonado3Aya Albittar4Natalie Wuliji5Ryan Basom6Yein Jeon7Qian Wu8Aiko Torkelson9Delaney Kirchmeier10Abigail Chutnik11Barbara Pender12Mohamed Sorror13Joshua A. Hill14Noam E. Kopmar15Rahul Banerjee16Andrew J. Cowan17Damian Green18Ajay K. Gopal19Christina Poh20Mazyar Shadman21Alexandre V. Hirayama22Brian G. Till23Erik L. Kimble24Lorenzo Iovino25Aude G. Chapuis26Folashade Otegbeye27Ryan D. Cassaday28Filippo Milano29Cameron J. Turtle30David G. Maloney31Jordan Gauthier32Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Department of Hematology, Hospital Clinic of Barcelona, Barcelona, SpainClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WADivision of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WADivision of Transplantation and Cellular Therapy, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FLClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAFaculty of Medicine and Health, The University of Sydney, Sydney, AustraliaClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA; Correspondence: Jordan Gauthier, Clinical Research Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Mail Stop D3-100, Seattle, WA 98109;Abstract: Immune effector cell–associated hematotoxicity (ICAHT) is associated with morbidity and mortality after chimeric antigen receptor (CAR) T-cell therapy. To date, the factors associated with ICAHT are poorly characterized, and there is no validated predictive model of ICAHT as defined by current consensus criteria. Therefore, we performed comprehensive univariate analyses to identify factors associated with severe (grade 3-4) early ICAHT (eICAHT) in 691 patients who received commercial or investigational CAR T-cell therapy for hematologic malignancies. In univariate logistic regression, preinfusion factors associated with severe eICAHT included disease type (acute lymphoblastic leukemia), prelymphodepletion (pre-LD) blood counts including absolute neutrophil count (ANC), lactate dehydrogenase (LDH), and inflammatory (C-reactive protein [CRP], ferritin, and interleukin-6 [IL-6]) and coagulopathy biomarkers (D-dimer). Postinfusion laboratory markers associated with severe eICAHT included early and peak levels of inflammatory biomarkers (CRP, ferritin, and IL-6), coagulopathy biomarkers (D-dimer), peak cytokine release syndrome grade, and peak neurotoxicity grade. We trained (n = 483) and validated (n = 208) 2 eICAHT prediction models (eIPMs): eIPMPre including preinfusion factors only (disease type and pre-LD ANC, platelet count, LDH, and ferritin) and eIPMPost containing both preinfusion (disease type and pre-LD ANC, platelet count, and LDH) and early postinfusion (day +3 ferritin) factors. Both models generated calibrated predictions and high discrimination (area under the receiver operating characteristic curve in test set, 0.87 for eIPMPre and 0.88 for eIPMPost), with higher net benefit in decision curve analysis for eIPMPost. Individualized predictions of severe eICAHT can be generated from both eIPMs using our online tool (available at https://eipm.fredhutch.org).http://www.sciencedirect.com/science/article/pii/S2473952924006876 |
| spellingShingle | Emily C. Liang Jennifer J. Huang Andrew J. Portuguese Valentín Ortiz-Maldonado Aya Albittar Natalie Wuliji Ryan Basom Yein Jeon Qian Wu Aiko Torkelson Delaney Kirchmeier Abigail Chutnik Barbara Pender Mohamed Sorror Joshua A. Hill Noam E. Kopmar Rahul Banerjee Andrew J. Cowan Damian Green Ajay K. Gopal Christina Poh Mazyar Shadman Alexandre V. Hirayama Brian G. Till Erik L. Kimble Lorenzo Iovino Aude G. Chapuis Folashade Otegbeye Ryan D. Cassaday Filippo Milano Cameron J. Turtle David G. Maloney Jordan Gauthier Development and validation of predictive models of early immune effector cell–associated hematotoxicity Blood Advances |
| title | Development and validation of predictive models of early immune effector cell–associated hematotoxicity |
| title_full | Development and validation of predictive models of early immune effector cell–associated hematotoxicity |
| title_fullStr | Development and validation of predictive models of early immune effector cell–associated hematotoxicity |
| title_full_unstemmed | Development and validation of predictive models of early immune effector cell–associated hematotoxicity |
| title_short | Development and validation of predictive models of early immune effector cell–associated hematotoxicity |
| title_sort | development and validation of predictive models of early immune effector cell associated hematotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924006876 |
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