Literature DB >> 34264268

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

Uri Greenbaum1, Paolo Strati2,3, Rima M Saliba1, Janet Torres1, Gabriela Rondon1, Yago Nieto1, Chitra Hosing1, Samer A Srour1, Jason Westin2, Luis E Fayad2, Hun J Lee2, Swaminathan P Iyer2, Ranjit Nair2, Loretta J Nastoupil2, Simrit Parmar2, Maria A Rodriguez2, Felipe Samaniego2, Raphael E Steiner2, Michael Wang2, Chelsea C Pinnix4, Christopher R Flowers2, Sudhakar Tummala5, Jeremy L Ramdial1, Fevzi F Yalniz1, Misha Hawkins2, Katayoun Rezvani1, Richard E Champlin1, Elizabeth J Shpall1, Sattva S Neelapu2, Partow Kebriaei1, Sairah Ahmed1,2.   

Abstract

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × 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 = .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 = .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.
© 2021 by The American Society of Hematology.

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Year:  2021        PMID: 34264268      PMCID: PMC8341350          DOI: 10.1182/bloodadvances.2021004575

Source DB:  PubMed          Journal:  Blood Adv        ISSN: 2473-9529


  25 in total

1.  EASIX and mortality after allogeneic stem cell transplantation.

Authors:  Thomas Luft; Axel Benner; Tobias Terzer; Sonata Jodele; Christopher E Dandoy; Rainer Storb; Lambros Kordelas; Dietrich Beelen; Ted Gooley; Brenda M Sandmaier; Mohamed Sorror; Markus Zeisbrich; Aleksandar Radujkovic; Peter Dreger; Olaf Penack
Journal:  Bone Marrow Transplant       Date:  2019-09-26       Impact factor: 5.483

2.  EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis.

Authors:  Thomas Luft; Axel Benner; Sonata Jodele; Christopher E Dandoy; Rainer Storb; Ted Gooley; Brenda M Sandmaier; Natalia Becker; Aleksandar Radujkovic; Peter Dreger; Olaf Penack
Journal:  Lancet Haematol       Date:  2017-07-18       Impact factor: 18.959

3.  Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells.

Authors:  Juliane Gust; Kevin A Hay; Laïla-Aïcha Hanafi; Daniel Li; David Myerson; Luis F Gonzalez-Cuyar; Cecilia Yeung; W Conrad Liles; Mark Wurfel; Jose A Lopez; Junmei Chen; Dominic Chung; Susanna Harju-Baker; Tahsin Özpolat; Kathleen R Fink; Stanley R Riddell; David G Maloney; Cameron J Turtle
Journal:  Cancer Discov       Date:  2017-10-12       Impact factor: 39.397

Review 4.  Chimeric antigen receptor T-cell therapy - assessment and management of toxicities.

Authors:  Sattva S Neelapu; Sudhakar Tummala; Partow Kebriaei; William Wierda; Cristina Gutierrez; Frederick L Locke; Krishna V Komanduri; Yi Lin; Nitin Jain; Naval Daver; Jason Westin; Alison M Gulbis; Monica E Loghin; John F de Groot; Sherry Adkins; Suzanne E Davis; Katayoun Rezvani; Patrick Hwu; Elizabeth J Shpall
Journal:  Nat Rev Clin Oncol       Date:  2017-09-19       Impact factor: 66.675

5.  Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.

Authors:  Sattva S Neelapu; Frederick L Locke; Nancy L Bartlett; Lazaros J Lekakis; David B Miklos; Caron A Jacobson; Ira Braunschweig; Olalekan O Oluwole; Tanya Siddiqi; Yi Lin; John M Timmerman; Patrick J Stiff; Jonathan W Friedberg; Ian W Flinn; Andre Goy; Brian T Hill; Mitchell R Smith; Abhinav Deol; Umar Farooq; Peter McSweeney; Javier Munoz; Irit Avivi; Januario E Castro; Jason R Westin; Julio C Chavez; Armin Ghobadi; Krishna V Komanduri; Ronald Levy; Eric D Jacobsen; Thomas E Witzig; Patrick Reagan; Adrian Bot; John Rossi; Lynn Navale; Yizhou Jiang; Jeff Aycock; Meg Elias; David Chang; Jeff Wiezorek; William Y Go
Journal:  N Engl J Med       Date:  2017-12-10       Impact factor: 91.245

6.  Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma.

Authors:  Frederick L Locke; John M Rossi; Sattva S Neelapu; Caron A Jacobson; David B Miklos; Armin Ghobadi; Olalekan O Oluwole; Patrick M Reagan; Lazaros J Lekakis; Yi Lin; Marika Sherman; Marc Better; William Y Go; Jeffrey S Wiezorek; Allen Xue; Adrian Bot
Journal:  Blood Adv       Date:  2020-10-13

7.  CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade.

Authors:  Theodoros Giavridis; Sjoukje J C van der Stegen; Justin Eyquem; Mohamad Hamieh; Alessandra Piersigilli; Michel Sadelain
Journal:  Nat Med       Date:  2018-05-28       Impact factor: 53.440

8.  Endothelial Activation and Stress Index (EASIX) at Admission Predicts Fluid Overload in Recipients of Allogeneic Stem Cell Transplantation.

Authors:  Ankur Varma; Gabriela Rondon; Samer A Srour; Julianne Chen; Celina Ledesma; Richard E Champlin; Stefan O Ciurea; Rima M Saliba
Journal:  Biol Blood Marrow Transplant       Date:  2020-02-09       Impact factor: 5.742

9.  Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

Authors:  Loretta J Nastoupil; Michael D Jain; Lei Feng; Jay Y Spiegel; Armin Ghobadi; Yi Lin; Saurabh Dahiya; Matthew Lunning; Lazaros Lekakis; Patrick Reagan; Olalekan Oluwole; Joseph McGuirk; Abhinav Deol; Alison R Sehgal; Andre Goy; Brian T Hill; Khoan Vu; Charalambos Andreadis; Javier Munoz; Jason Westin; Julio C Chavez; Amanda Cashen; N Nora Bennani; Aaron P Rapoport; Julie M Vose; David B Miklos; Sattva S Neelapu; Frederick L Locke
Journal:  J Clin Oncol       Date:  2020-05-13       Impact factor: 50.717

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  10 in total

Review 1.  CAR T Cell Therapy in Hematological Malignancies: Implications of the Tumor Microenvironment and Biomarkers on Efficacy and Toxicity.

Authors:  Jing Yuan Tan; Muhammed Haiqal Low; Yunxin Chen; Francesca Lorraine Wei Inng Lim
Journal:  Int J Mol Sci       Date:  2022-06-22       Impact factor: 6.208

Review 2.  Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.

Authors:  Shakira J Grant; Alyssa A Grimshaw; Juliet Silberstein; Donna Murdaugh; Tanya M Wildes; Ashley E Rosko; Smith Giri
Journal:  Transplant Cell Ther       Date:  2022-03-11

3.  The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL.

Authors:  Kai Rejeski; Ariel Perez; Gloria Iacoboni; Olaf Penack; Veit Bücklein; Liv Jentzsch; Dimitrios Mougiakakos; Grace Johnson; Brian Arciola; Cecilia Carpio; Viktoria Blumenberg; Eva Hoster; Lars Bullinger; Frederick L Locke; Michael von Bergwelt-Baildon; Andreas Mackensen; Wolfgang Bethge; Pere Barba; Michael D Jain; Marion Subklewe
Journal:  J Immunother Cancer       Date:  2022-05       Impact factor: 12.469

4.  Transformed Lymphoma Is Associated with a Favorable Response to CAR-T-Cell Treatment in DLBCL Patients.

Authors:  Anna Nydegger; Urban Novak; Marie-Noëlle Kronig; Myriam Legros; Sacha Zeerleder; Yara Banz; Ulrike Bacher; Thomas Pabst
Journal:  Cancers (Basel)       Date:  2021-12-02       Impact factor: 6.639

5.  Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma.

Authors:  Paolo F Caimi; Gabriela Pacheco Sanchez; Ashish Sharma; Folashade Otegbeye; Nausheen Ahmed; Patricio Rojas; Seema Patel; Sarah Kleinsorge Block; Jennifer Schiavone; Kayla Zamborsky; Kirsten Boughan; Antoinette Hillian; Jane Reese-Koc; Mikhail Maschan; Boro Dropulic; Rafick-Pierre Sekaly; Marcos de Lima
Journal:  Front Immunol       Date:  2021-10-12       Impact factor: 7.561

6.  Editorial: Platelets in Disease: From Biomarkers Discovery to Therapeutic Targets.

Authors:  Fan Zhao; Si Zhang; Shenghui Zhang
Journal:  Front Pharmacol       Date:  2022-02-14       Impact factor: 5.810

7.  EASIX and Severe Endothelial Complications After CD19-Directed CAR-T Cell Therapy-A Cohort Study.

Authors:  Felix Korell; Olaf Penack; Mike Mattie; Nicholas Schreck; Axel Benner; Julia Krzykalla; Zixing Wang; Michael Schmitt; Lars Bullinger; Carsten Müller-Tidow; Peter Dreger; Thomas Luft
Journal:  Front Immunol       Date:  2022-04-08       Impact factor: 8.786

8.  Increased visceral fat distribution and body composition impact cytokine release syndrome onset and severity after CD19 chimeric antigen receptor T-cell therapy in advanced B-cell malignancies.

Authors:  David M Cordas Dos Santos; Kai Rejeski; Michael Winkelmann; Lian Liu; Paul Trinkner; Sophie Günther; Veit L Bücklein; Viktoria Blumenberg; Christian Schmidt; Wolfgang G Kunz; Michael Von Bergwelt-Baildon; Sebastian Theurich; Marion Subklewe
Journal:  Haematologica       Date:  2022-09-01       Impact factor: 11.047

9.  EASIX, Modified EASIX and Simplified EASIX as an Early Predictor for Intensive Care Unit Admission and Mortality in Severe COVID-19 Patients.

Authors:  Aleksander Zińczuk; Marta Rorat; Krzysztof Simon; Tomasz Jurek
Journal:  J Pers Med       Date:  2022-06-21

Review 10.  Cardiovascular disease and chimeric antigen receptor cellular therapy.

Authors:  Anjali Rao; Andrew Stewart; Mahmoud Eljalby; Praveen Ramakrishnan; Larry D Anderson; Farrukh T Awan; Alvin Chandra; Srilakshmi Vallabhaneni; Kathleen Zhang; Vlad G Zaha
Journal:  Front Cardiovasc Med       Date:  2022-09-23
  10 in total

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