Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy
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...
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MDPI AG
2023-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/11/3058 |
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| author | Katja Seipel Mariesol Abbühl Ulrike Bacher Henning Nilius Michael Daskalakis Thomas Pabst |
| author_facet | Katja Seipel Mariesol Abbühl Ulrike Bacher Henning Nilius Michael Daskalakis Thomas Pabst |
| author_sort | Katja Seipel |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.06), overall survival was 37 vs. 8 months (<i>p</i> = 0.11), complete response rates were 51% vs. 30% (<i>p</i> = 0.05), and refractory disease rates were 14% vs. 32% (<i>p</i> = 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. |
| first_indexed | 2024-03-11T03:11:01Z |
| format | Article |
| id | doaj.art-df6fda3249ee4f86aa89469d7124be61 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:11:01Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-df6fda3249ee4f86aa89469d7124be612023-11-18T07:40:08ZengMDPI AGCancers2072-66942023-06-011511305810.3390/cancers15113058Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell TherapyKatja Seipel0Mariesol Abbühl1Ulrike Bacher2Henning Nilius3Michael Daskalakis4Thomas Pabst5Department for Biomedical Research, University of Bern, 3008 Bern, SwitzerlandDepartment of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, SwitzerlandDepartment of Hematology, Inselspital, Bern University Hospital, 3010 Bern, SwitzerlandDepartment of Clinical Chemistry, Inselspital, Bern University Hospital, 3010 Bern, SwitzerlandDepartment of Hematology, Inselspital, Bern University Hospital, 3010 Bern, SwitzerlandDepartment of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, SwitzerlandChimeric 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 (<i>p</i> = 0.06), overall survival was 37 vs. 8 months (<i>p</i> = 0.11), complete response rates were 51% vs. 30% (<i>p</i> = 0.05), and refractory disease rates were 14% vs. 32% (<i>p</i> = 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.https://www.mdpi.com/2072-6694/15/11/3058B-lymphocyte antigen CD19single nucleotide polymorphism (SNP)minor allele frequency (MAF)CAR-T cell therapyFMC63-chimeric antigen receptor (FMC63-CAR)Tisagenlecleucel (Kymriah©) |
| spellingShingle | Katja Seipel Mariesol Abbühl Ulrike Bacher Henning Nilius Michael Daskalakis Thomas Pabst Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy Cancers B-lymphocyte antigen CD19 single nucleotide polymorphism (SNP) minor allele frequency (MAF) CAR-T cell therapy FMC63-chimeric antigen receptor (FMC63-CAR) Tisagenlecleucel (Kymriah©) |
| title | Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy |
| title_full | Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy |
| title_fullStr | Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy |
| title_full_unstemmed | Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy |
| title_short | Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy |
| title_sort | clinical impact of single nucleotide polymorphism in cd 19 on treatment outcome in fmc63 car t cell therapy |
| topic | B-lymphocyte antigen CD19 single nucleotide polymorphism (SNP) minor allele frequency (MAF) CAR-T cell therapy FMC63-chimeric antigen receptor (FMC63-CAR) Tisagenlecleucel (Kymriah©) |
| url | https://www.mdpi.com/2072-6694/15/11/3058 |
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