Key points are not available for this paper at this time.
Background and Importance The prognosis for relapsed/refractory(R/R) Mantle cell lymphoma (MCL), a mature B-cell lymphoma, after the failure of Bruton tyrosine kinase inhibitors (BTKi) remains unfavourable. Brexucabtagene autoleucel, an autologous anti-CD19 CAR T-cell therapy, represents the first FDA-EMA approved CAR-T treatment for BTKi-refractory R/R MCL. Here, we describe a challenging case of haematologic toxicity associated with immune effector cell-associated syndrome (ICANS). Aim and Objectives The patient is a 59-year-old with refractory mantle cell lymphoma, initially treated with six alternating cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-DAHP (rituximab, cisplatin, cytarabine, and dexamethasone), followed by autologous stem cell transplantation. In the second-line, the patient received ibrutinib, and in the third-line, Brexucabtagene autoleucel. Material and Methods The patient experienced grade≥3 cytokine release syndrome (CRS), treated with tocilizumab and steroids, and immune effector cell-associated neurotoxicity syndrome (ICANS), with neurological symptoms such as worsened handwriting, significant attention and orientation decline, necessitating the administration of 20 mg dexamethasone and, for refractoriness, 100 mg anakinra every 6 hours. Results The combined therapy resulted in rapid improvement of the patient's toxicity, leading to discharge from the intensive care unit. The therapy was definitively discontinued after 5 days. PET and CT scans showed complete remission of the lymphoma. As the adoption of CAR-T therapy in haematology increases, the management of side effects becomes crucial. ICANS is a common toxicity, particularly in patients treated with axicabtagene ciloleucel and brexucabtagene celeucel, with a median onset time of 6–8 days. In this case, ICANS lasted 25 days, but the combination of dexamethasone and anakinra proved effective. The use of anakinra, an IL-1 receptor antagonist approved for rheumatoid arthritis, was first examined for refractory CRS/ICANS in a murine model before entering clinical practice at various CAR-T centres. The administration of anakinra, in conjunction with dexamethasone, has shown benefits in managing severe ICANS. A phase 2 study (NCT4205838) aims to gather solid evidence for its application. Initial results from the study, based on seven patients, show potential in reducing severe ICANS and corticosteroid use. Conclusion and Relevance In conclusion, CAR T-cell therapy offers innovative treatment for B-cell malignancies but introduces unique toxicity. Careful monitoring and interventions are essential to ensure patient safety. Anakinra shows promise in ICANS management and reducing corticosteroid use. References and/or Acknowledgements Conflict of Interest No conflict of interest.
Menardi et al. (Fri,) studied this question.