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Infectious Complications Following CD30 Chimeric Antigen Receptor T-Cell Therapy in Adults

Cao, F.; Xiu, Y.; Mohnasky, M.; Serody, J. S.; Armistead, P.; Dotti, G.; Smith, M.; Huggins, J.; Messina, J.; Ramachandran, B.; Saullo, J.; Stromberg, J.; Saha, M. K.; Walsh, M.; Savoldo, B.; Grover, N.; Henderson, H. I.; Andermann, T. M.

2024-07-11 hematology
10.1101/2024.07.10.24310235 medRxiv
Show abstract

Infections are increasingly recognized as a common complication of chimeric antigen receptor (CAR) T-cell therapy. The incidence of clinically-defined infection after CD19.CAR T-cell therapy for relapsed/refractory lymphoma ranges from 60-90% in the first year after CAR T-cell therapy and is the most common cause for non-relapse mortality. However, infectious risk after CAR T-cell therapy targeting other malignancies is not well understood. Herein, we report for the first time, infectious complications after CD30.CAR T-cell treatment for patients with Hodgkins lymphoma and peripheral T-cell lymphoma. Since CD30 is only expressed on a subset of activated T and B-cells, we hypothesized that CD30.CAR T-cell patients would have reduced incidence and severity of infections after infusion compared to CD19.CAR T-cell patients. We retrospectively evaluated all 64 patients who received CD30.CAR T-cells at a single institution between 2016-2021, and assessed infections within one year after cell infusion, comparing these data to a contemporary cohort of 50 patients who received CD19.CAR T-cells at the same institution between 2018-2021. 23 CD30.CAR T-cell patients (36%) and 18 CD19.CAR T-cell patients (36%) developed a microbiologically confirmed infection. Infection severity and bacterial infections were higher in the CD19.CAR T-cell group compared to CD30.CAR T-cell recipients who more commonly had grade 1 respiratory viral infections. Our data reflect expected outcomes for severity and infection type in CD19.CAR T-cell patients and provide a benchmark for comparison with the novel CD30.CAR T-cell product. Although our findings require replication in a larger cohort, they have implications for antimicrobial prophylaxis guidelines after CD30.CAR T-cell therapy. KEY POINTS1) The incidence of infections within the first year after CD30.CAR T-cell therapy was equivalent to that following CD19.CAR T-cell therapy 2) Viral infections were more common after CD30.CAR T-cell therapy but bacterial infections predominated after CD19.CAR T-cell therapy.

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