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Poster session 14

769P - Analysis of PMS2 mutation as a potential biomarker for melanoma immunotherapy

Date

10 Sep 2022

Session

Poster session 14

Topics

Tumour Immunology

Tumour Site

Melanoma

Presenters

Jiaming Qiu

Citation

Annals of Oncology (2022) 33 (suppl_7): S331-S355. 10.1016/annonc/annonc1058

Authors

J.`. Qiu1, Q. Zhang2, Y. Tan2, Q. Duan2, C. Qi2, T. Sun2

Author affiliations

  • 1 Department Of Pathology, ChangShu No.2 People's Hospital, 215500 - Changshu/CN
  • 2 The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., 210042 - Nanjing/CN
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Abstract 769P

Background

Several clinical trials have demonstrated that mismatch repair deficiency is significantly associated with long-term immunotherapy-related responses in malignancies treated with immune checkpoint inhibitors (ICIs). The protein encoded by PMS2 gene is a key component of the mismatch repair system. However, whether the PMS2 mutation status is associated with better survival benefit in ICIs treatment melanoma is still unclear.

Methods

Firstly, 418 melanoma samples derived from seven immunotherapy studies (http://www.cbioportal.org/), as discovery cohort, were used to evaluate association between PMS2 mutation and efficacy of immunotherapy. Then the predictive value of PMS2 was validated in 320 melanoma patients from MSKCC cohort (http://www.cbioportal.org/). TMB was calculated as the total count of nonsynonymous mutations in coding sequence.

Results

In discovery cohort, compared to PMS2-wildtype group, longer overall survival (OS) was observed in the PMS2-mutant group (median OS: not reach, NR vs 22.7 months, HR= 0.13, 95% CI: 0.02 to 0.95, P = 0.011). In addition, PMS2-mutant group had higher TMB than wildtype group (median [IQR]: 58.68 [IQR: 44.01-114.4] vs. 6.37 [IQR, 2.15-14.64], P<0.001). In validation cohort, PMS2-mutant patients also achieved significantly longer OS compared with PMS2-wildtype patients (median OS: NR vs. 42.0 months, HR=0, 95% CI: 0.37 to 0.69, P=0.044). Moreover, in validation cohort, compared with PMS2-wildtype group, PMS2-mutant group also had high TMB (median [IQR]: 18.69 [10.82-42.38] vs. 8.85[3.51-23.52]). Multivariable analysis of validation cohort demonstrated that PMS2 mutation was associated with better OS (HR= 0.10; 95%CI, 0.01-0.71; P = 0.021), after adjusting for age, gender, metastasis type, ICI type.

Conclusions

The results indicate that PMS2 somatic mutation is associated with high TMB in melanoma. Analysis of discovery and validation cohort data shows PMS2 mutation is associated with better OS in ICI-treated patients. These findings indicates that PMS2 mutation may serve as a potential predictive biomarker for ICIs in melanoma.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

ChangShu No. 2 People's Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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