So I think in the past three years, we have gained a lot of experience in management of early and late toxicities of CD19 CAR-T therapy, mainly in patients treated with DLBCL, but also in patients with MCL and BCP-ALL. We differentiate in early toxicities, so toxicities occurring in the first 30 days and late toxicities that occur post 30 days, post-transfusion, and the early toxicities are mainly CRS and ICANS, immune cell effector neurotoxicity syndrome, which occur in variable frequencies after CAR-T therapy depending on CAR-T product, dose, disease entity, tumor burden, pro-inflammatory markers, to mention some of the risk factors that have been identified so far...
So I think in the past three years, we have gained a lot of experience in management of early and late toxicities of CD19 CAR-T therapy, mainly in patients treated with DLBCL, but also in patients with MCL and BCP-ALL. We differentiate in early toxicities, so toxicities occurring in the first 30 days and late toxicities that occur post 30 days, post-transfusion, and the early toxicities are mainly CRS and ICANS, immune cell effector neurotoxicity syndrome, which occur in variable frequencies after CAR-T therapy depending on CAR-T product, dose, disease entity, tumor burden, pro-inflammatory markers, to mention some of the risk factors that have been identified so far. And I’d like to highlight two aspects in this context, first, looking at the clinical trial data, but also as real-world evidence, the incidence of higher grade CRS is markedly decreasing mostly due to the growing experience of treating physicians and early intervention with tocilizumab and steroids. And second, we are still trying to identify individual risk factors for the development of CRS. And I think eventually we will move into stratifying patients for an outpatient setting, inpatient setting, inpatient setting intermediate care unit, or normal ward. And I think we have to further develop risk factors that can better stratify and our group could show that BMI and abdominal visceral adipose tissue or waist to height ratio also contributes as a risk factor for the development of early onset and severity of CRS. This interestingly also correlated to higher peak IL-6 levels suggesting that adipose tissue contributes to the inflammatory state of these patients and for the development of CRS. I think this might be one of the examples where we better understand which patients will develop CRS and we can better and further stratify.