Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy

  • Cancers (Basel). 2023 Jun 5;15(11):3058. doi: 10.3390/cancers15113058.
Katja Seipel  1 ,  Mariesol Abbühl  2 ,  Ulrike Bacher  3 ,  Henning Nilius  4 ,  Michael Daskalakis  3 ,  Thomas Pabst  2
Affiliations
  • 1. Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland.
  • 2. Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
  • 3. Department of Hematology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
  • 4. Department of Clinical Chemistry, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
PMID: 37297020 DOI: 10.3390/cancers15113058
Abstract

Chimeric antigen receptor (CAR)-T cell therapy is effective in patients with relapsed or refractory Diffuse Large B-cell Lymphoma (r/r DLBCL) with response rates of 63-84% and complete response observed in 43-54%. Common germline variants of the target antigen CD19 may elicit different responses to CAR-T cell therapy. The CD19 gene single nucleotide polymorphism rs2904880 encoding leucine or valine at amino acid position 174 of the CD19 antigen was prevalent in 51% of the studied DLBCL patients. In a retrospective comparative analysis of clinical outcome, there were significant differences in CD19 L174 versus V174 carriers: the median time of progression-free survival was 22 vs. 6 months (p = 0.06), overall survival was 37 vs. 8 months (p = 0.11), complete response rates were 51% vs. 30% (p = 0.05), and refractory disease rates were 14% vs. 32% (p = 0.04). The single nucleotide polymorphism in CD19 was shown to influence the treatment outcome in FMC63-anti-CD19-CAR-T cell therapy, and the CD19 minor allele L174 predicted a favorable treatment outcome.

Keywords
Axicaptagene ciloleucel (Yescarta©); B-lymphocyte antigen CD19; CAR-T cell therapy; FMC63-chimeric antigen receptor (FMC63-CAR); Lisocabtagene maraleucel (Breyanzi©); Tisagenlecleucel (Kymriah©); minor allele frequency (MAF); single nucleotide polymorphism (SNP).
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