Circulating AMC and gene signature of monocytes used to predict benefit for CAR T-cell therapy in LBCL
Carniti C, Caldarelli NM, Agnelli L, et al. Monocytes in Leukapheresis Products Affect the Outcome of CD19-Targeted CAR T-Cell Therapy in Lymphoma Patients. Blood Advances. 2024; (doi: 10.1182/bloodadvances.2024012563).
Scientists have developed a new model that identifies individuals with relapsed/refractory large B-cell lymphomas (R/R LBCL) who are poor candidates for CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. Sustained remission is elusive in this patient community, with 6 out of 10 recipients either relapsing or never mounting a response at all. The ability to predict who might benefit from CD19 CAR T therapy is valuable from a clinical standpoint and also could avert unnecessary spending on costly CAR T-cell treatment. To explore, researchers launched a prospective, observational study involving 95 patients with R/R LBCL. Transcriptomic and functional evaluations of leukapheresis products exposed a shared gene signature in participants with abbreviated progression-free survival (PFS). The four myeloid genes in the signature are expressed by T cells isolated from leukapheresis products, demonstrating how monocytes influence CAR T therapy response. In fact, elevated absolute monocyte counts (AMCs) at the time of leukapheresis had negative implications for both treatment response and PFS. The model considers circulating AMC and the gene signature at leukapheresis together to predict PFS in LBCL patients undergoing anti-CD19 CAR T-cell treatment. Investigators believe monocyte depletion strategies could improve outcomes.