Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile.
atrial arrhythmias
cardiotoxicity
cardio‐oncology
chimeric antigen receptor T cell
immunotherapy
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
12 May 2024
12 May 2024
Historique:
received:
27
01
2024
accepted:
18
04
2024
medline:
13
5
2024
pubmed:
13
5
2024
entrez:
12
5
2024
Statut:
aheadofprint
Résumé
Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67-5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39-19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72-18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA282987
Pays : United States
Informations de copyright
© 2024 British Society for Haematology and John Wiley & Sons Ltd.
Références
June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73.
Cancer.gov. CAR T cells: engineering patients' immune cells to treat their cancers 2023.
Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, et al. GPRC5D‐targeted CAR T cells for myeloma. N Engl J Med. 2022;387:1196–1206.
Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384:705–716.
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B‐cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396:839–852.
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B‐cell lymphoma. N Engl J Med. 2019;380:45–56.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B‐cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–448.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T‐cell therapy in refractory large B‐cell lymphoma. N Engl J Med. 2017;377:2531–2544.
Oluwole OO, Bishop MR, Gisselbrecht C, Gordon LI, Kersten MJ, Maloney DG, et al. ZUMA‐7: a phase 3 randomized trial of axicabtagene ciloleucel (Axi‐Cel) versus standard‐of‐care (SOC) therapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL). J Clin Oncol. 2018;36:TPS7585.
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second‐line treatment in patients with relapsed or refractory large B‐cell lymphoma (TRANSFORM): results from an interim analysis of an open‐label, randomised, phase 3 trial. Lancet. 2022;399:2294–2308.
Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, et al. Tisagenlecleucel vs standard of care as second‐line therapy of primary refractory or relapsed aggressive B‐cell non‐Hodgkin lymphoma: analysis of the phase III Belinda study. Blood. 2021;138:LBA‐6.
Dada R. Understanding the differences in outcome between CART studies as second‐line treatment in aggressive lymphoma. J Oncol Pharm Pract. 2023;29:183–190.
Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383:2255–2273.
Brammer JE, Braunstein Z, Katapadi A, Porter K, Biersmith M, Guha A, et al. Cardiovascular toxicity and clinical outcomes following chimeric antigen receptor T‐cell infusion (CART) for lymphoid malignancies. Biol Blood Marrow Transplant. 2020;26:S270.
Goldman A, Maor E, Bomze D, Liu JE, Herrmann J, Fein J, et al. Adverse cardiovascular and pulmonary events associated with chimeric antigen receptor T‐cell therapy. J Am Coll Cardiol. 2021;78:1800–1813.
Mahmood SS, Riedell PA, Feldman S, George G, Sansoterra SA, Althaus T, et al. Biomarkers and cardiovascular outcomes in chimeric antigen receptor T‐cell therapy recipients. Eur Heart J. 2023;44:2029–2042.
Alvi RM, Frigault MJ, Fradley MG, Jain MD, Mahmood SS, Awadalla M, et al. Cardiovascular events among adults treated with chimeric antigen receptor T‐cells (CAR‐T). J Am Coll Cardiol. 2019;74:3099–3108.
Ganatra S, Redd R, Hayek SS, Parikh R, Azam T, Yanik GA, et al. Chimeric antigen receptor T‐cell therapy–associated cardiomyopathy in patients with refractory or relapsed non‐Hodgkin lymphoma. Circulation. 2020;142:1687–1690.
Lefebvre B, Kang Y, Smith AM, Frey NV, Carver JR, Scherrer‐Crosbie M. Cardiovascular effects of CAR T cell therapy: a retrospective study. JACC CardioOncol. 2020;2:193–203.
Steiner RE, Banchs J, Koutroumpakis E, Becnel M, Gutierrez C, Strati P, et al. Cardiovascular events in patients treated with chimeric antigen receptor T‐cell therapy for aggressive B‐cell lymphoma. Haematologica. 2022;107:1555–1566.
Tonorezos ES, Stillwell EE, Calloway JJ, Glew T, Wessler JD, Rebolledo BJ, et al. Arrhythmias in the setting of hematopoietic cell transplants. Bone Marrow Transplant. 2015;50:1212–1216.
Lyon AR, López‐Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler‐Klein J, et al. 2022 ESC guidelines on cardio‐oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio‐Oncology Society (IC‐OS): developed by the task force on cardio‐oncology of the European Society of Cardiology (ESC). Eur Heart J. 2022;43:4229–4361.
Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, et al. Management of immune‐related adverse events in patients treated with chimeric antigen receptor T‐cell therapy: ASCO guideline. J Clin Oncol. 2021;39:3978–3992.
Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31:171–190.
Epperla N, Kumar A, Abutalib SA, Awan FT, Chen YB, Gopal AK, et al. ASTCT clinical practice recommendations for transplantation and cellular therapies in diffuse large B cell lymphoma. Transplant Cell Ther. 2023;29:548–555.
FDA Adverse Event Reporting System (FAERS) Public Dashboard|FDA [Internet].
Bonora BM, Raschi E, Avogaro A, Fadini GP. SGLT‐2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system. Cardiovasc Diabetol. 2021;20:39.
Poluzzi E, Raschi E, Piccinni C, De Ponti F. Data mining techniques in pharmacovigilance: analysis of the publicly accessible FDA adverse event reporting system (AERS). Data Mining Applications in Engineering and Medicine. InTech; 2012. https://doi.org/10.5772/50095
Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.
Writing Group Members, January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society. Heart Rhythm. 2019;16:e66–e93.
Page RL, Joglar JA, Caldwell MA, Calkins H, Conti JB, Deal BJ, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society. Heart Rhythm. 2016;13:e92–e135.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non‐Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–3068.
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625–638.
Bate A, Evans SJW. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf. 2009;18:427–436.
Bate A, Lindquist M, Edwards IR, Olsson S, Orre R, Lansner A, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol. 1998;54:315–321.
Harpaz R, DuMouchel W, LePendu P, Bauer‐Mehren A, Ryan P, Shah NH. Performance of pharmacovigilance signal‐detection algorithms for the FDA adverse event reporting system. Clin Pharmacol Ther. 2013;93:539–546.
Raschi E, Poluzzi E, Salvo F, Pariente A, de Ponti F, Marchesini G, et al. Pharmacovigilance of sodium‐glucose co‐transporter‐2 inhibitors: what a clinician should know on disproportionality analysis of spontaneous reporting systems. Nutr Metab Cardiovasc Dis. 2018;28:533–542.
Chang EK, Chanson D, Teh JB, Iukuridze A, Peng K, Forman SJ, et al. Atrial fibrillation in patients undergoing allogeneic hematopoietic cell transplantation. J Clin Oncol. 2021;39:902–910.
Walkey AJ, Wiener RS, Ghobrial JM, Curtis LH, Benjamin EJ. Incident stroke and mortality associated with new‐onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA. 2011;306:2248–2254.
Xiao FP, Chen MY, Wang L, He H, Jia ZQ, Kuai L, et al. Outcomes of new‐onset atrial fibrillation in patients with sepsis: a systematic review and meta‐analysis of 225,841 patients. Am J Emerg Med. 2021;42:23–30.
Lin M‐H, Kamel H, Singer DE, Wu YL, Lee M, Ovbiagele B. Perioperative/postoperative atrial fibrillation and risk of subsequent stroke and/or mortality: a meta‐analysis. Stroke. 2019;50:1364–1371.
Guha A, Jain A, Aggarwal A, Dey AK, Dani S, Ganatra S, et al. Length of stay and cost of care associated with admissions for atrial fibrillation among patients with cancer. BMC Cardiovasc Disord. 2022;22:272.
Weinkove R, George P, Dasyam N, McLellan AD. Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations. Clin Transl Immunology. 2019;8:e1049.
Salter AI, Ivey RG, Kennedy JJ, Voillet V, Rajan A, Alderman EJ, et al. Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function. Sci Signal. 2018;11:eaat6753.
Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA. CD28 costimulation: from mechanism to therapy. Immunity. 2016;44:973–988.
Börschel CS, Ortega‐Alonso A, Havulinna AS, Jousilahti P, Salmi M, Jalkanen S, et al. Inflammatory proteomics profiling for prediction of incident atrial fibrillation. Heart. 2023;109(13):1000–1006.
Dobrev D, Heijman J, Hiram R, Li N, Nattel S. Inflammatory signalling in atrial cardiomyocytes: a novel unifying principle in atrial fibrillation pathophysiology. Nat Rev Cardiol. 2023;20:145–167.
Scott L Jr, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation. Int J Cardiol. 2019;287:195–200.
Wang EY, Hulme OL, Khurshid S, Weng LC, Choi SH, Walkey AJ, et al. Initial precipitants and recurrence of atrial fibrillation. Circ Arrhythm Electrophysiol. 2020;13:e007716.