Abstract 1503P
Background
Letetresgene autoleucel is a genetically engineered NY-ESO-1–specific TCR T-cell therapy being investigated in mSS patients whose tumours express the NY-ESO-1 antigen and who are HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06 allele positive (NY+/HLA+). Our objective was to understand the prevalence & clinical characteristics of NY+/HLA+ mSS patients in a nationally representative population.
Methods
This was a retrospective cohort study in French national reference centres. Adult patients with histologically confirmed diagnosis of mSS ≥1 Jan 2000 and registered in the French sarcoma database (NETSARC+) with available FFPE archival primary tumour samples & clinical data were included. Tumour samples were examined for NY-ESO-1 expression (by IHC, NY+ defined as ≥30% tumour cells staining with 2+/3+ stain intensity) & HLA sub-type (by RNA-seq using Optitype genotyping algorithm).
Results
109 mSS patients met study criteria; with NY-ESO-1 expression available for 106, HLA status for 94, and both statuses for 91 patients. 61% of patients were NY+ with similar NY+ prevalence among HLA+ and HLA- populations (56% and 62%, resp) and by line of systemic treatment (in 1L: 60%, 2L: 59%). Mean age of tumour samples was 11.0 years (NY+ 10.4 yrs, NY- 12.0 yrs, p=0.151). 45% of patients were HLA+ with similar HLA+ prevalence among NY+ and NY- populations (43% and 49%, resp) and by line (in 1L: 44%, 2L: 45%). Overall, 25% (23/91) were dual positive (NY+/HLA+, in 1L: 23%, 2L: 22%). Characteristics of NY+/HLA+ vs. NY- and/or HLA- patients reported in table. Table: 1503P
| Patient and tumour characteristics | All (n=109), includes 17 patients with missing NY/HLA data | NY+/HLA+ (n=23) in primary tumour samples | NY- and/or HLA- (n=69) in primary tumour samples | Fisher exact test (p>0.05 = NS) |
| Male | 55% | 61% | 58% | NS |
| Primary tumour location = limbs | 60% | 87% | 49% | p=0.003 |
| Primary tumour size ≥90 mm | 57% | 70% | 56% | NS |
| Diagnosed with metastatic disease ≤55 yrs age | 71% | 78% | 68% | NS |
| Site of first metastasis = lung only | 70% | 91% | 67% | p=0.029 |
| Only one metastatic site | 87% | 96% | 86% | NS |
| Diagnosed with metastatic disease ≤ year 2010 | 45% | 65% | 41% | NS |
| Time from localised to metastatic diagnosis ≤12 months | 29% | 41% | 29% | NS |
Conclusions
Nationally representative prevalence and clinical profile of mSS patients with NY+/HLA+ tumours were previously unknown and have been documented by this study. Among primary tumour samples, no relationship was observed between NY-ESO expression and age of samples, HLA sub-type, or line of treatment.
Clinical trial identification
Editorial acknowledgement
Editorial support in the form of copyediting and collating author comments was provided by Travis Taylor, George Chappell, and Joanna Lamprou at Scion and was funded by GSK.
Legal entity responsible for the study
GSK.
Funding
GSK.
Disclosure
A. Dufresne: Non-Financial Interests, , Project Lead, Translational research project: GSK, Adaptimmune; Non-Financial Interests, , Project Lead, Translational research program: Bayer. M. Woessner: Financial Interests, Institutional, Full or part-time Employment: GSK; Financial Interests, Institutional, Stocks/Shares: GSK. E. Klohe: Financial Interests, Institutional, Stocks/Shares, Oversaw NY-ESO-1 assay validation planning and report used in the study to determine NY-ESO-1 status; Review study outputs and contribute to assay descriptions in study report.: GSK. T. Thayaparan: Financial Interests, Institutional, Funding: GSK; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: GSK; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Institutional, Stocks/Shares: GSK; Financial Interests, Institutional, Leadership Role: Precision Cancer Consortium. K. Blouch: Financial Interests, Institutional, Other, Chair: Precision Cancer Consortium; Financial Interests, Institutional, Other, Other financial interests: GSK. I. Eleftheriadou: Financial Interests, Institutional, Stocks/Shares: GSK. M.J. Nathenson: Financial Interests, Institutional, Full or part-time Employment: GSK; Financial Interests, Personal and Institutional, Other, Support to attend ASCO and CTOS: GSK, Dana-Farber Cancer Institute; Financial Interests, Institutional, Stocks/Shares: GSK, Bristol Myers Squibb, Johnson & Johnson, Merck. S. Pokras: Financial Interests, Personal, Stocks/Shares: GSK; Financial Interests, Institutional, Full or part-time Employment: GSK. All other authors have declared no conflicts of interest.