Journal article
Association of Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) with response and outcomes in patients with urothelial carcinoma (UC) treated with Immune Checkpoint Inhibitor (ICI)
Clinical genitourinary cancer, Vol.22(6), 102198
12/2024
DOI: 10.1016/j.clgc.2024.102198
PMID: 39241315
Abstract
Background
Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI.
Methods
Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable.
Results
We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months).
Conclusions
Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.
Details
- Title: Subtitle
- Association of Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) with response and outcomes in patients with urothelial carcinoma (UC) treated with Immune Checkpoint Inhibitor (ICI)
- Creators
- Dimitra Rafailia Bakaloudi - University of WashingtonRafee Talukder - Baylor College of MedicineDimitrios Makrakis - Albert Einstein College of MedicineLeonidas Diamantopoulos - Mayo ClinicThomas Enright - University of WashingtonJacob B. Leary - University of WashingtonUbenthira Patgunarajah - Cleveland ClinicVinay Mathew Thomas - University of UtahUmang Swami - University of UtahNeeraj Agarwal - University of UtahTanya Jindal - University of California, San FranciscoVadim S. Koshkin - University of California, San FranciscoJason R. Brown - University Hospitals Seidman Cancer CenterPedro Barata - University Hospitals Seidman Cancer CenterJure Murgic - Sisters of Charity HospitalMarija Miletić - Sisters of Charity HospitalJeffrey Johnson - Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA, USAYousef Zakharia - University of IowaGavin Hui - David Geffen School of Medicine at UCLAIgnacio Duran - Marqués de Valdecilla University HospitalAlexandra Drakaki - David Geffen School of Medicine at UCLALucia Alonso Buznego - Marqués de Valdecilla University HospitalRafael Morales Barrera - Universitat Autònoma de BarcelonaDavid Marmolejo Castañeda - Hebron UniversityMacarena Rey-Cárdenas - Hospital Universitario 12 De OctubreDaniel Castellano - Hospital Universitario 12 De OctubreCharles B. Nguyen - University of MichiganJoseph J. Park - University of MichiganAjjai Alva - University of MichiganRana R. McKay - University of California San DiegoTyler F. Stewart - University of California San DiegoIlana B. Epstein - Harvard Medical SchoolJoaquim Bellmunt - Harvard Medical SchoolJonathan L. Wright - University of WashingtonShilpa Gupta - Cleveland ClinicPetros Grivas - University of WashingtonAli Raza Khaki - Stanford University
- Resource Type
- Journal article
- Publication Details
- Clinical genitourinary cancer, Vol.22(6), 102198
- DOI
- 10.1016/j.clgc.2024.102198
- PMID
- 39241315
- NLM abbreviation
- Clin Genitourin Cancer
- ISSN
- 1558-7673
- eISSN
- 1938-0682
- Publisher
- Elsevier Inc
- Grant note
DR Bakaloudi acknowledges support from KureIt Cancer Research. P Grivas and J Wright acknowledge the Seattle Transla-tional Tumor Research program. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This research did not receive other external funding.
- Language
- English
- Electronic publication date
- 08/12/2024
- Date published
- 12/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984696783502771
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