Combining CAR T-cell therapy with cytokine signaling blockers to boost outcomes in AML

Bhagwat AS, Torres L, Shestova O, et al. Cytokine-Mediated CAR T Therapy Resistance in AML. Nature Medicine. 2024; (doi: 10.1038/s41591-024-03271-5).

Researchers report that while autologous chimeric antigen receptor (CAR) T-cell manufacturing is possible in the setting of acute myeloid leukemia (AML), myeloid-supporting cytokines released during CAR-T treatment affect efficacy. These cytokines promote AML blast survival via kinase signaling, which in turn mediates CAR T-cell exhaustion. This resistance mechanism observed in AML is not seen in B cell malignancies, which have benefited greatly from CAR therapy. The researchers propose that using CAR T-cell therapies in tandem with cytokine signaling blockers might be an effective method of improving immunotherapy efficacy and garnering more favorable outcomes in AML patients. The low clinical efficacy of CAR-T in AML is illustrated in a pilot study that infused 12 adults with relapsed/refractory AML with anti-CD123 CAR T cells. Only 3 of the 12 achieved clinical response, while 10 of the 12 presented with cytokine release syndrome.
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