PS1222 IL‐6 ASSOCIATED WITH GRADING OF CYTOKINE RELEASE SYNDROME AND MANAGEMENT TIME OF TOCILIZUMAB AFTER CAR‐T CELL THERAPY
Authors: Li C. , Mei H. , Hu Y. , Guo T. , Liu L. , Ai L. , Jiang H. , Tang L. , Deng J. 
Published: June 2019

Background:

Cytokine release syndrome(CRS) is the most prominent and serious toxicity of the CAR T cell therapy. It still lacks of the measurable indicator for CRS grading scales. The IL‐6 receptor blocker, like tocilizumab, can effectively relieve CRS. However, the optimal management time of tocilizumab is not yet determined, especially about prophylactic administration.

Aims:

1.To evaluate the relationship between the peak level and time of serum cytokines and the CRS grading. 2.To assess the association between the level of serum cytokines and the efficacy of the CAR‐T cell therapy. 3.To investigate the optimal management time of tocilizumab in the grading 2 CRS based on the level of serum IL‐6.

Methods:

34 patients were enrolled in the study, including 27 ALL patients and 4 DLBCL patients treated with anti‐CD19 CAR‐T cells and 3 MM patients with anti‐BCMA and anti‐CD38 CAR‐T cells. All the patients were monitored with serum cytokines, including IL‐6, IL‐2, IL‐10 and TNFα every day for one month after theinfusion of CAR‐T cells and the toxicity was graded by CTCAE 5.0. We analyzed the relationships between the peak level and time of serum cytokines and the CRS grading. The association between the peak level of serum cytokines and the efficacy of the CAR‐T cell therapy was also assessed. At the same time, we compared the optimal management time of tocilizumab in the grading 2 CRS based on the level of serum IL‐6. Kruskal‐Wallis tests or one‐way ANOVA were used to compare the difference between two or more independent samples. P < 0.05 was regarded significance.

Results:

The peak level of IL‐6 and IL‐10 increased with the CRS grade(P < 0.001) and there is no obvious association between the peak level of IL‐2(P = 0.82) and TNFα(P = 0.32) and CRS grade. The peak level of IL‐6 and IL‐10 of Grade 0 and Grade 0 was ≤ twice the upper limit, Grade 2 ≤ 20 times the upper limit and Grade 3 and Grade 4 ≥ 200 times the upper limit. Only the occurrence time of the peak IL‐6 raised with CRS grade(P = 0.048). The occurrence time of the peak IL‐6 of Grade 0 and Grade 0 was around the 6th day, Grade 2 and Grade 3 near the 10th day and Grade 4 the 12nd day. Except IL‐2(P = 0.005), no significant relationship between the the peak level of IL‐6(P = 0.972), IL‐10(P = 0.995) and TNFα(P = 0.420) and the efficacy of the CAR‐T cell therapy. The peak level of IL‐2 of no response was higher than partial or complete remission. 3/10 of patients with Grade 2 CRS were administered with tocilizumab(80 mg) and one patient with lower peak level of IL‐6 progressed with neurotoxicity. The other two patients with ≥ 30 times the upper limit of IL‐6 were relieved. All the 9 patients with Grade 3 and Grade 4, whose peak level of IL‐6 were ≥ 200 times the upper limit, were given with tocilizumab(160 mg or 240 mg) and under remission.

Summary/Conclusion:

Our research demonstrates a positive correlation between thepeak level and time ofserum IL‐6 and the CRS grade. The level of serum IL‐6 is an important consideration for the administration of tocilizumab in the early stage of CRS, which can effectively avoid some adverse reactions such as CRES. (NCT02965092, ChiCTR1800018143)

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