Background and Importance Treatment with CD19-targeted chimeric antigen receptor T-cells (CAR-T) is transforming the therapeutic landscape of some B-cell malignancies, achieving high rates of responses. However, they have a new toxicity profile identified in the clinical trials, related to T-cell hyperactivation, namely cytokine release syndrome (CRS) and Immune effector cell-Associated Neurotoxicity Syndrome (ICANS). Hospital Pharmacists should continue generating knowledge about these adverse effects (AEs) in real-life population.
Aim and Objectives Describing the toxicity profile of CAR-T cells therapies in a cohort of real-life patients and looking for possible risk factors related to current and previous treatments.
Material and Methods All patients infused with anti-CD19 CAR-T therapies in our centre between 01/01/2019 and 21/07/2022, out of clinical trials, were retrospectively analysed. We collected different descriptive variables of the patient, their pathology, CRS and ICANS type AEs, and treatments against them. For the statistics, proportion comparison tests and multivariate logistic regression were performed.
Results 88 patients were included (mean age 54.5 years, 44.3% women), 92.0% treated for B lymphomas and 8.0% for acute lymphoblastic leukemias. 56.8% received axicabtagene ciloleucel and 43.2% tisagenlecleucel, with 2.46 (1–6) previous lines received on average. About AEs, 79 (89.8%) patients suffered CRS (38.0% of them grades 2 to 4) and 31 (35.2%) ICANS (58.1% grades 2 to 4). The proportion of CRS was significantly higher (diff=55.5%, p>0.001), but, on the other hand, when the AE had occurred, the probability of it being grade 2–4 was significantly higher for ICANS than for CRS (diff=20.1%, p<0.05).
Concerning treatments employed, 77.1% of patients received tocilizumab, 61.4% corticosteroids (18.2% bolus doses), 27.3% siltuximab, and 19.2% anakinra. 53 (60.2%) patients required 2 or more treatments. Performing logistic regression, we found no significant risk factors for CRS, while having received tocilizumab, using axicabtagene ciloleucel, and suffering previous CRS grades 2–4 were associated with increased risk of ICANS (OR=6.72, 4.46, and 4.45 respectively, p<0.05).
Conclusion and Relevance Our real-life study supported the conclusions of other authors. After infusing a CAR-T, it was more likely to suffer CRS than ICANS, but, if it occurred, ICANS was more likely to be more severe. Suffering ICANS seems to be associated with previous tocilizumab use, axicabtagene ciloleucel, and previous moderate-severe CRS.
Conflict of Interest No conflict of interest
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