Cell reports. Medicine · 2022
A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Fahrmann Johannes F, Saini Neeraj Y, Chia-Chi Chang, Irajizad Ehsan, Strati Paolo, Nair Ranjit, Fayad Luis E, Ahmed Sairah, Lee Hun Ju, Iyer Swaminathan, Steiner Raphael, Vykoukal Jody, Wu Ranran, Dennison Jennifer B, Nastoupil Loretta, Jain Preetesh, Wang Michael, Green Michael, Westin Jason, Blumenberg Viktoria, Davila Marco, Champlin Richard, Shpall Elizabeth J, Kebriaei Partow, Flowers Christopher R, Jain Michael, Jenq Robert, Stein-Thoeringer Christoph K, Subklewe Marion, Neelapu Sattva S, Hanash Sam
Аннотация
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed or refractory (r/r) large B cell lymphoma (LBCL) results in durable response in only a subset of patients. MYC overexpression in LBCL tumors is associated with poor response to treatment. We tested whether an MYC-driven polyamine signature, as a liquid biopsy, is predictive of response to anti-CD19 CAR-T therapy in patients with r/r LBCL. Elevated plasma acetylated polyamines were associated with non-durable response. Concordantly, increased expression of spermidine synthase, a key enzyme that regulates levels of acetylated spermidine, was prognostic for survival in r/r LBCL. A broad metabolite screen identified additional markers that resulted in a 6-marker panel (6MetP) consisting of acetylspermidine, diacetylspermidine, and lysophospholipids, which was validated in an independent set from another institution as predictive of non-durable response to CAR-T therapy. A polyamine centric metabolomics liquid biopsy panel has predictive value for response to CAR-T therapy in r/r LBCL.