Abstract
Clinical trials have confirmed that chimeric antigen receptor (CAR) T cell therapies are revolutionizing approaches for treating several relapsed or refractory hematological tumors. Cytokine release syndrome (CRS) is an adverse event with high incidence during CAR-T treatment. A further understanding of the characteristics and related risk factors of CRS is important for effective management. A total of 142 patients with relapsed or refractory acute lymphocyte leukemia (ALL), lymphoma, or multiple myeloma (MM) received lymphodepletion chemotherapy followed by infusion of CAR-T cells. The characteristics of CRS at different time points after treatment were monitored and risk factors were analyzed. The incidence of CRS for ALL, lymphoma, and multiple myeloma were 82%, 90%, and 90% respectively. Fever was observed on a median of day 3 for ALL, day 1 for lymphoma, and day 8.5 for MM after CAR-T cell infusion, and the duration was different between grade 1–2 CRS and grade 3–5 CRS. Disease types, peak concentration of IL-6, and CRP were associated with CRS. For patients with ALL, numbers of lymphoblast in bone marrow before lymphodepletion, peak concentration of IL-6, and CRP were independent risk factors of CRS. Clinical stage of lymphoma patients and high tumor burden in marrow of MM patients were independent risk factors of CRS. In conclusion, the characteristics and risk factors of CRS in different B-cell hematological tumors are different and should be managed individually during CAR-T cell therapy.
Highlights
Clinical trials have confirmed that chimeric antigen receptor (CAR)-T has become an important approach for treating relapse or refractory hematological tumors [1,2,3]
All MM patients received a combination of humanized anti-CD19 and anti-BCMA CAR T cells treatment
Univariate analysis showed that the number of blasts cells in bone marrow (p=0.003), serum peak concentration of IL-6 (p=0.001) and C-reactive protein (CRP) (p=0.008), and minimum value of CD4/CD8 (p=0.028) are the influencing factors for the occurrence of Cytokine release syndrome (CRS). These factors were further entered into an ordinal logistic regression model, and the results showed that the number of blasts in bone marrow (OR:1.034, 95% CI 1.011-1.058) was the independent risk factors for CRS (Table 4, Table S3)
Summary
Clinical trials have confirmed that CAR-T has become an important approach for treating relapse or refractory hematological tumors [1,2,3]. Adverse events in CAR-T treatment are a major obstacle that can even cause death. CRS is one of the adverse events with high incidence in CAR-T cell treatment [4]. According to the published data, more than 54–91% of patients may develop different grades of CRS during treatment [5]. It is important to improve the prognosis through evaluation of severity and timely intervention of CRS. Currently available diagnostic criteria and severity grading systems of CRS are based on clinical manifestations that may delay the diagnosis and treatment of CRS [6]. A deep understanding of the characteristics of CRS and related risk factors has great clinical significance for effective management
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have