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5PSQ-065 Intestinal perforation after CRS and ICANS in a Car-T treated patient: a clinical case report
  1. G Menardi1,
  2. G Tarasco1,
  3. A Castellino2,
  4. M Viglione1,
  5. ME Bersia1,
  6. M Allione1,
  7. D Degioanni1,
  8. S Gastaldi1,
  9. L Infante1,
  10. E Grande1,
  11. C Fruttero1
  1. 1Azienda Ospedaliera Santa Croce e Carle, Hospital Pharmacy- Azienda Ospedaliera Santa Croce e Carle, Cuneo, Italy
  2. 2Azienda Ospedaliera Santa Croce e Carle, Haematology- Azienda Ospedaliera Santa Croce e Carle, Cuneo, Italy


Background and Importance Brexucabtagene autoleucel, an autologous anti-CD19 CAR T-cell therapy with a chimeric antigen receptor (CAR), represents the first FDA-EMA approved CAR-T for relapsed/refractory mantle cell lymphoma (MCL). While CAR T-cell therapy is an innovation, it also comes with unique toxicities.

Aim and Objectives Here, we describe the case of a patient with relapsed-refractory mantle cell lymphoma treated with brexucabtagene autoleucel who experienced Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), evaluated with a Naranjo scale score of 5–8, and intestinal perforation in the days following therapy. This abstract has been written in order to share the clinical difficulties of CAR-T patient management and to highlight the potential role of anti-IL6 medicines in this singular adverse drug reaction.

Material and Methods The patient received tocilizumab and dexamethasone for CRS, effectively managing it but faced substantial ICANS symptoms. Anakinra and high-dose dexamethasone led to notable improvement. On day +34, acute abdominal symptoms emerged, leading to a CT scan revealing diverticulitis complications, necessitating exploratory laparotomy and colonic resection. Remarkably, histological analysis showed no lymphoma or extensive CAR T-cell infiltration but revealed neutrophilic inflammation and Cytomegalovirus (CMV) presence, treated with antivirals.

Results With the increasing adoption of CAR-T therapy in haematology, the accurate management of side effects becomes crucial. A search in our country’s pharmacovigilance database did not reveal other reports of intestinal perforation possibly related to tocilizumab in patients treated with brexucabtagene autoleucel apart from this case, evaluated with a score of 1–4 on the Naranjo scale. Clinical-data and post-marketing surveillance have reported an increased risk of gastrointestinal perforation in patients treated with axicabtagene ciloleucel, but there have been no reports of intestinal perforation associated with brexucabtagene autoleucel. However, the setting remains similar: patients undergo lymphodepleting chemotherapy and receive a high dose of IL-6 receptor inhibitor and corticosteroids.

Conclusion and Relevance Intestinal perforation in CAR-T treated patients is mentioned in the ESMO-guidelines for the management of Immune Effector Cell-Associated Hypersensitivity (ICAH) and a correlation between tocilizumab and intestinal perforations has been suggested (5–8 Naranjo scale score), as observed in clinical trials and post-marketing analysis among patients with rheumatoid arthritis. This case underscores the importance of meticulous monitoring and understanding CAR-T therapy intricacies and toxicity management.

Conflict of Interest No conflict of interest.

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