Germline thrombophilia gene alterations and thrombosis rates among patients with advanced germ cell tumors treated with chemotherapy.

Authors

Landon Brown

Landon Carter Brown

Levine Cancer Institute, Atrium Health, Charlotte, NC

Landon Carter Brown , Myra M. Robinson , Michael Joseph McCormack Jr., Nury Steuerwald , James Thomas Symanowski , Rupali Bose , Brittany Neelands , Tobi Akinyelu , Chad Livasy , Wencheng Li , Nathanael C. Haynes , Claud Grigg , Derek Raghavan , Peter E Clark , Jai Narendra Patel , Earle F Burgess

Organizations

Levine Cancer Institute, Atrium Health, Charlotte, NC, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston Salem, NC

Research Funding

Institutional Funding
Atrium Health Foundation

Background: Men with advanced germ cell tumors (GCT) treated with cisplatin-based chemotherapy are at high risk of venous thromboembolism (VTE). Validated predictors of VTE would allow development of targeted prophylactic anticoagulation strategies in this population. We hypothesized that a high genomic risk score from a previously identified panel of germline single nucleotide polymorphisms (SNPs) in thrombophilia genes would be associated with an increased risk of VTE within 6 months of chemotherapy initiation for GCT. Methods: Men with stage IIA or higher GCT who received 3-4 cycles of cisplatin-based chemotherapy were identified at two centers with available tissue for germline sequencing. High genomic risk was defined as having 4 or more risk alleles from an established 5 SNP germline panel composed of ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865), and F11 (rs2036914). Univariable and multivariable logistic regression were used to evaluate the impact of genomic risk on VTE incidence within six months of chemotherapy initiation. Results: 123 patients were identified with 72% having non-seminoma histology and 28% categorized as IGCCCG intermediate or poor risk. The VTE rate was 26% (32/123), and the incidence of high genomic risk was 21% (26/123). Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5 – 3.5, p = 0.54). A multivariable model identified Khorana score, N3 status and elevated LDH as predictors for VTE (Table). The association between high genomic risk and VTE strengthened when adjusting for clinical variables, but remained non-significant, adjusted OR 2.1 (95% CI 0.7 – 6.5, p = 0.18). The optimal threshold to define high genomic risk in this cohort was 3 or more risk alleles, adjusted OR 2.5 (95% CI 0.9 – 6.8, p = 0.08). ABO (non-O blood type) was the only individual SNP significantly associated with VTE (p < 0.01). Conclusions: In this multi-institutional cohort, a previously established germline thrombophilia panel was not clearly associated with increased VTE risk among patients with GCT receiving chemotherapy. Khorana score, elevated LDH, clinical nodal stage, and non-O blood type were the strongest predictors of VTE. Exploratory analysis of the association between VTE risk and 76 additional SNPs is ongoing. Prospective studies of prophylactic anticoagulation are warranted in high-risk patients with advanced GCT undergoing chemotherapy.

Select variablesUnivariable OR95% CIp-valueMultivariable OR95% CIp-value
Genomic risk (high vs low)1.40.5 – 3.5.542.10.7 – 6.5.18
Khorana score ( > 1 vs 1)3.81.6 – 8.8< .012.61.01 – 6.7.05
N Stage (N3 vs < N3)4.01.7 – 9.4< .012.40.9 – 6.5.09
LDH ( > 1.5x vs < 1.5x ULN)6.22.5 – 15.1< .013.91.3 – 11.1.01

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Genitourinary Cancer—Prostate, Testicular, and Penile

Track

Genitourinary Cancer—Prostate, Testicular, and Penile

Sub Track

Germ Cell/Testicular Cancer

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr e17023)

DOI

10.1200/JCO.2023.41.16_suppl.e17023

Abstract #

e17023

Abstract Disclosures