CRP and ferritin in addition to the EASIX score predict CAR-T–related toxicity

Abstract

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study’s objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T–related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.

Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma

“…While tumor burden is associated with risk of severe CRS in NHL, several groups are investigating the use of baseline, pre – lymphodepletion laboratory parameters as risk predictors of CRS and ICANS. More recently, investigators have evaluated the use of the Endothelial Activation and Stress Index (EASIX) [lactate dehydrogenase (U/L(x creatinine (mg/dL)/platelet count (10 9 cells/L)] ( 40 ), with either use of CRP concentration instead of creatinine (modified EASIX, mEASIX) ( 41 ) or in combination with ferritin and CRP concentrations (EASIX-FC) ( 42 ). These modifications of the EASIX score can predict the risk of CRS and) ICANS and mEASIX can also predict disease response ( 41 ).…”

Transformed Lymphoma Is Associated with a Favorable Response to CAR-T-Cell Treatment in DLBCL Patients

“…While some factors have already been identified for their correlation with prognosis, the prognostic factors for response to CAR-T-cell therapy are a matter of ongoing research [ 12 , 13 , 14 ]. Among them, a lower LDH level before lymphodepleting therapy preceding CAR-T-cell infusion was associated with superior progression-free survival [ 12 , 13 ], while the achievement of remission within the first three months after CAR-T-cell therapy was shown to be associated with a durable response [ 5 , 17 , 19 ]. Other parameters, e.g., whether distinct lymphoma subtypes respond better to CAR-T-cell therapy than others, currently remain unclear.…”

“…Despite the rapidly increasing number of clinical reports, uncertainty remains regarding the factors that impact clinical outcomes after CAR-T-cell treatment [ 4 , 5 , 6 , 12 , 13 , 14 , 15 ]. In particular, it remains unclear whether distinct lymphoma subtypes may differ in their response to CAR-T-cell treatment [ 1 , 6 , 7 , 16 , 17 , 18 ]. For example, a recent report suggested that patients with a history of follicular lymphoma had a better progression-free course than patients with DLBCL [ 16 ].…”

Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences

“…Endothelial cell damage and capillary leak are clinical hallmarks of CRS ( Figure 1 ). The endothelial activation and stress index (EASIX) is defined as [(creatinine level × lactate dehydrogenase (LDH)) level/peripheral blood platelet count], and this marker of endothelial activation has been validated in the CAR-T cell therapy setting [ 53 ]. This study included patients who received treatment with CAR-T cells, and the authors investigated the association between EASIX and the immune effector cell-associated neurotoxicity syndrome (ICANS) in a group of 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma.…”

“…As stated above the EASIX index has also been investigated as a possible biomarker in combination with CRP and ferritin [ 53 ]. This index could identify three different patient subsets regarding development of CRS Grades 2–4 with 74%, 51%, and 29% cumulative incidences.…”