CD19 CAR-T Cells(Hebei Taihe Chunyu Biotechnology)

Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are complications of CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy. The Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) scores have been retrospectively proven to be predictive of CRS and ICANS in adult CAR T-cell recipients. However, these scores have not been evaluated in pediatric cohorts. We retrospectively report on 76 pediatric and adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia treated with CD19-CAR T cells at St. Jude Children’s Research Hospital or Johns Hopkins Hospital. Data included patient, disease, and treatment characteristics. EASIX and m-EASIX scores were calculated at days –5 before, 0, and +3 after CAR T-cell infusion. CRS and ICANS occurred in 47 and 17 patients, respectively. At all evaluated time points, the median EASIX scores were higher for patients who developed severe CRS and any grade ICANS, and the median m-EASIX scores were higher in patients who developed severe CRS and severe ICANS than those with no/mild CRS/ICANS. Receiver operating characteristic curve analysis showed that both scores were strong predictors of CRS, especially severe CRS, at all time points. Any grade and severe ICANS were best predicted by both scores at day +3. m-EASIX uniformly outperformed EASIX, except for predicting any grade ICANS. Our results validate the potential utility of EASIX and m-EASIX scores for predicting CAR T-cell–related complications for pediatric and AYA patients.

In 2024, CD19-CAR T cells are ubiquitous in rheumatology, with incredible therapeutic results in cases of severe and refractory disease. This major advance confirms the interest of the B lymphocyte as a therapeutic target, and also suggests the real possibility of a drug-free remission, at the price of minor and minimal side effects for the time being. However, the necessary perspective is still lacking for a therapy that remains out of reach because of its price. On the other hand, the availability of targeted treatments offering real corticosteroid sparing benefits seems imminent for gigantocellular arteritis and polymyalgia rheumatica, with very promising results and treatments already used on a daily basis, notably JAK inhibitors, anti-IL17 and sarilumab.