Cytokine and Chemokines as Predictive Biomarkers of CAR-T Therapy Outcomes in Large B-Cell Lymphoma
Among patients undergoing anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of large B-cell lymphoma (LBCL), plasma cytokines and chemokines may serve as predictive biomarkers for treatment response and toxicity, according to study results published in Clinical Lymphoma, Myeloma & Leukemia.
Previous research has found CAR-T therapy has been associated with significant toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients with LBCL. Researchers aimed to identify biomarker profiles associated with CAR-T outcomes and adverse events, including CRS and ICANS.
Overall, 24 LBCL patients treated with CAR-T therapy were evaluated. Plasma levels of 47 cytokines and chemokines were analyzed at multiple time points: pre-lymphodepletion, day 0 (infusion), and post-infusion. At infusion, higher levels of IL-7 and CCL8 and IL-21 were associated with improved remission rates, as well as higher levels of IL-21 at day 7.
Additionally, an increased risk for CRS was associated with higher CCL17 at day 0 higher CCL13, IL-6, and IFN-γ at day 3. Increased risk for ICANS was linked to elevated day 0 TGF-β1 and Day 3 IL-5 and IL-7. Elevated TGF-β1 at day 0 and IL-5 or IL-7 at day 3 were also associated with increased risk for ICANS. Conversely, lower levels of CCL19 at day 0 and lower VIP at day 3 were associated with a higher risk for ICANS.
"These findings highlight the role of plasma cytokines and chemokines as biomarkers for predicting both the therapeutic efficacy and toxicity of CART, with the potential to guide more personalized, safer, and effective immunotherapies for B-cell lymphoma," the researchers concluded.
Source:
Zeng F, Zhang H, Wang S, et al. Plasma cytokine and chemokine profiles predict efficacy and toxicity of anti-CD19 CAR-T Cell therapy in large B-cell lymphoma. Clinical Lymphoma Myeloma and Leukemia. Published online February 20, 2025. doi: 10.1016/j.clml.2025.02.009
