Multiple Ulcers with Perforations of the Small Intestine in the Acute Phase of CD19 Chimeric Antigen Receptor T-cell Therapy Possibly Associated with Tocilizumab Administration

Overview

Journal Intern Med

Date 2025 Feb 2

PMID 39894508

Authors

Yasutaka Masuda

Akira Honda

Yoichi Yasunaga

Mineo Kurokawa

Affiliations

Soon will be listed here.

Abstract

CD19 chimeric antigen receptor (CAR) T-cell therapy is associated with potentially life-threatening immunological toxicities. We herein report an 81-year-old woman who experienced multiple perforations in the small intestine 8 days after tisagenlecleucel infusion for relapsed and refractory follicular lymphoma with no gastrointestinal involvement. A pathological examination of the resected small intestine revealed multiple ulcers that formed after resection but without lymphoma involvement. Based on these findings, tocilizumab used for cytokine release syndrome was considered to be associated with these lesions. This case illustrates a previously undescribed but serious sequela of CAR T-cell therapy, calling for relevant personnel to be vigilant about gastrointestinal symptoms.

References

Ozaka S, Fukuda M, Takahashi H, Tsutsumi K, Iwao M, Hirashita Y . Tocilizumab-induced mucosal injury in the terminal ileum mimicking intestinal Behçet's disease: A case report. Medicine (Baltimore). 2023; 102(25):e34118. PMC: 10289693. DOI: 10.1097/MD.0000000000034118. View

Schiff M, Kremer J, Jahreis A, Vernon E, Isaacs J, van Vollenhoven R . Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011; 13(5):R141. PMC: 3308069. DOI: 10.1186/ar3455. View

Saad E, Awadelkarim A, Agab M, Babkir A . Tocilizumab-Associated Small Bowel Perforation in a Young Patient With Rheumatoid Arthritis: A Lesson to Remember During COVID-19 Pandemic. J Med Cases. 2022; 13(3):135-139. PMC: 8929210. DOI: 10.14740/jmc3902. View

Pfeil J, Grulich-Henn J, Wenning D, Breil T, Gunther P, Lutz T . Multiple upper gastrointestinal perforations in a 15-year-old patient treated with tocilizumab. Rheumatology (Oxford). 2014; 53(9):1713-4. DOI: 10.1093/rheumatology/keu032. View

Kuhn K, Manieri N, Liu T, Stappenbeck T . IL-6 stimulates intestinal epithelial proliferation and repair after injury. PLoS One. 2014; 9(12):e114195. PMC: 4257684. DOI: 10.1371/journal.pone.0114195. View

Bruce-Hickman D, Sajeed S, Pang Y, Seow C, Chen W, Gulati Kansal M . Bowel ulceration following tocilizumab administration in a COVID-19 patient. BMJ Open Gastroenterol. 2020; 7(1). PMC: 7437943. DOI: 10.1136/bmjgast-2020-000484. View

Hayden P, Roddie C, Bader P, Basak G, Bonig H, Bonini C . Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European.... Ann Oncol. 2021; 33(3):259-275. DOI: 10.1016/j.annonc.2021.12.003. View

Cappell K, Kochenderfer J . Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol. 2023; 20(6):359-371. PMC: 10100620. DOI: 10.1038/s41571-023-00754-1. View

Ohkubo A, Osoegawa T, Harada N, Iboshi Y, Sumida Y, Nakamuta M . A Rare Case of Rheumatoid Arthritis with Tocilizumab-induced Intestinal Mucosal Injury. Intern Med. 2021; 61(7):1011-1014. PMC: 9038478. DOI: 10.2169/internalmedicine.8031-21. View

10.

Monemi S, Berber E, Sarsour K, Wang J, Lampl K, Bharucha K . Incidence of Gastrointestinal Perforations in Patients with Rheumatoid Arthritis Treated with Tocilizumab from Clinical Trial, Postmarketing, and Real-World Data Sources. Rheumatol Ther. 2016; 3(2):337-352. PMC: 5127961. DOI: 10.1007/s40744-016-0037-z. View

11.

Cortes-Bullich A, Perez A, Bachmeier C, Mhaskar R, Chavez J, Shah B . Outcomes of CD19 Chimeric Antigen Receptor T Cell Therapy in Patients with Gastrointestinal Tract Involvement of Large B Cell Lymphoma. Transplant Cell Ther. 2021; 27(9):768.e1-768.e6. PMC: 8403629. DOI: 10.1016/j.jtct.2021.05.018. View

12.

Fusaroli M, Isgro V, Cutroneo P, Ferrajolo C, Cirillo V, Del Bufalo F . Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database. Drug Saf. 2022; 45(8):891-908. PMC: 9360149. DOI: 10.1007/s40264-022-01194-z. View

13.

Xie F, Yun H, Bernatsky S, Curtis J . Brief Report: Risk of Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologic Treatments. Arthritis Rheumatol. 2016; 68(11):2612-2617. PMC: 5538140. DOI: 10.1002/art.39761. View

14.

Strangfeld A, Richter A, Siegmund B, Herzer P, Rockwitz K, Demary W . Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. Ann Rheum Dis. 2016; 76(3):504-510. PMC: 5445993. DOI: 10.1136/annrheumdis-2016-209773. View

15.

van der Meer P, Ypma P, van Geloven N, van Hilten J, van Wordragen-Vlaswinkel R, Eissen O . Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial. Blood. 2018; 132(2):223-231. DOI: 10.1182/blood-2018-02-831289. View

15.

Morris E, Neelapu S, Giavridis T, Sadelain M . Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol. 2021; 22(2):85-96. PMC: 8127450. DOI: 10.1038/s41577-021-00547-6. View

16.

Barbulescu A, Delcoigne B, Askling J, Frisell T . Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study. RMD Open. 2020; 6(2). PMC: 7425111. DOI: 10.1136/rmdopen-2020-001201. View

17.

Rempenault C, Lukas C, Combe B, Herrero A, Pane I, Schaeverbeke T . Risk of diverticulitis and gastrointestinal perforation in rheumatoid arthritis treated with tocilizumab compared to rituximab or abatacept. Rheumatology (Oxford). 2021; 61(3):953-962. DOI: 10.1093/rheumatology/keab438. View

18.

Beauvais D, Karleskind O, Loridant S, Nyga R, Lamiaux M, Moreau A . Potential role of tocilizumab in severe gastrointestinal barrier damage after CAR T-cell therapy. J Microbiol Immunol Infect. 2021; 54(2):327-330. DOI: 10.1016/j.jmii.2021.02.006. View