HLA genotyping in synovial sarcoma: Identifying HLA-A*02 and its association with clinical outcome Journal Article
| Authors: | Rosenbaum, E.; Seier, K.; Bandlamudi, C.; Dickson, M.; Gounder, M.; Keohan, M. L.; Chi, P.; Kelly, C.; Movva, S.; Nacev, B.; Simeone, N.; Donoghue, M.; Slotkin, E. K.; Qin, L. X.; Antonescu, C. R.; Tap, W. D.; D'Angelo, S. P. |
| Article Title: | HLA genotyping in synovial sarcoma: Identifying HLA-A*02 and its association with clinical outcome |
| Abstract: | Purpose: To determine if a targeted exome panel utilizing matched normal DNA can accurately detect germline and somatic HLA genes in patients with synovial sarcoma (SS) and whether select HLA-A*02 genotypes are prognostic or predictive of outcome in metastatic SS. Experimental Design: Patients with metastatic SS consented to HLA typing by a Clinical Laboratory Improvement Amendments (CLIA)-certified test to determine eligibility for a clinical trial of NY-ESO-1-specific engineered T cells restricted to carriers of HLAA* 02:01,-A*02:05, or-A*02:06 (HLA-A*02 eligible). HLA genotype was determined from Memorial Sloan Kettering Integrated Molecular Profiling of Actionable Cancer Targets (MSK-IMPACT), where feasible, and somatic loss of heterozygosity (LOH) in HLA alleles was identified. Overall survival (OS) was estimated and stratified by HLA-A*02 eligibility. Results: A total of 23 patients had HLA genotyping by a CLIA-certified lab and MSK-IMPACT. Ninety percent (108/ 110) of the sequenced alleles were concordant between IMPACT and the outside lab. LOH of HLA genes was detected in three tumors, one had loss of HLA-A*02:01. In total, 66 patients were screened for T-cell therapy and 20 (30%) were HLA-A *02 eligible on outside testing. Univariate analysis of OS from the time of metastasis found HLA-A *02 eligibility was marginally associated with shorter OS [HR = 1.95; 95% confidence interval (CI), 0.995-3.813; P = 0.052]. On multivariate analysis, older age and larger tumor size, but not HLA-A*02 eligibility, were significantly associated with decreased OS. HLA-A *02 eligibility did not impact OS after chemotherapy or pazopanib in the metastatic setting. Conclusions: Targeted gene panels like MSK-IMPACT may accurately report HLA type and identify loss of somatic HLA alleles. In a multivariable model, HLA-A*02 eligibility was not significantly associated with OS in patients with metastatic SS. |
| Keywords: | chemotherapy; antigen expression; pazopanib; follow-up; mutations; soft-tissue sarcoma; ny-eso-1; multicenter; blockade; prognostic-factor |
| Journal Title: | Clinical Cancer Research |
| Volume: | 26 |
| Issue: | 20 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2020-10-15 |
| Start Page: | 5448 |
| End Page: | 5455 |
| Language: | English |
| ACCESSION: | WOS:000582352800020 |
| DOI: | 10.1158/1078-0432.Ccr-20-0832 |
| PROVIDER: | wos |
| PMCID: | PMC7572879 |
| PUBMED: | 32816945 |
| Notes: | Article -- Source: Wos |
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