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Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With

Dimitra Rafailia Bakaloudi1, Rafee Talukder2, Dimitrios Makrakis3

  • 1Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.

Clinical Genitourinary Cancer
|September 6, 2024
PubMed
Abstract

Insights

High tumor mutational burden (TMB) and microsatellite instability-high (MSI-H) status may predict longer survival in urothelial carcinoma patients treated with immune checkpoint inhibitors (ICI), particularly with maintenance avelumab. Further validation is required.

Area of Science:

  • Oncology
  • Immunotherapy
  • Biomarkers

Background:

  • Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are established biomarkers for predicting immune checkpoint inhibitor (ICI) efficacy.
  • Urothelial Carcinoma (UC) is a significant cancer where ICI therapy is increasingly utilized.

Purpose of the Study:

  • To investigate the association between TMB and MSI status with patient survival in urothelial carcinoma (UC) treated with ICI monotherapy.
  • To evaluate TMB as both a dichotomous and continuous variable in relation to overall survival (OS).

Main Methods:

  • Retrospective analysis of 411 UC patients from 15 institutions treated with ICI monotherapy.
  • Overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) were primary and secondary endpoints.
  • TMB was assessed dichotomously (≥10 vs. <10 mut/Mb) and continuously; MSI status (MSI-H vs. MSI-S) was also analyzed.

Main Results:

  • In first-line/upfront ICI treatment, patients with TMB ≥10 mut/Mb showed numerically longer median OS (35 vs. 26 months).
  • A statistically significant association was observed between continuous TMB and OS (HR = 0.96, P = .01).
  • In patients receiving maintenance avelumab (mAV), high TMB (≥10 mut/Mb) was significantly associated with longer OS (61 vs. 17 months; HR = 0.2, P = .02).

Conclusions:

  • While not always statistically significant across all subsets, high TMB and MSI-H status were numerically associated with improved OS in UC patients receiving ICI.
  • The association was particularly pronounced in patients treated with maintenance avelumab (mAV).
  • Further prospective studies are warranted to validate these findings.
Keywords:
BiomarkersBladder cancerGenomicsImmunotherapyUrothelial carcinoma

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