A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma

Cell Rep Med. 2022 Nov 15;3(11):100720. doi: 10.1016/j.xcrm.2022.100720.

Abstract

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.

Keywords: CAR-T cell therapy; biomarker; large B cell lymphoma; liquid biopsy; metabolites; prognostic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD19
  • Cell- and Tissue-Based Therapy
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Polyamines
  • Receptors, Chimeric Antigen*

Substances

  • Receptors, Chimeric Antigen
  • Polyamines
  • Antigens, CD19