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
08/2024
DOI: 10.1016/j.clgc.2024.102198
Abstract
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.
Patients from 15 institutions were treated with ICI monotherapy (in any setting). 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.
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 vs TMB <10: mOS 35 vs 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=0.01). For 2+L: mOS was numerically longer in patients with TMB≥10 vs TMB<10: (20 vs 12 months; HR=0.9) and in patients with MSI-H and MSI-S was 12 vs 17 months, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB≥10 vs TMB <10: 61 vs 17 months; (HR = 0.2, p=0.02) and with MSI-H and MSI-S (NR vs 24 months).
Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Findings may have been inconclusive due to limited power and further validation is needed.
Micro-Abstract: Based on published data, 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 response and survival in patients with advanced urothelial carcinoma treated with ICI in a “real-world” setting. High TMB and MSI were associated with better outcomes consistent with prior data.
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 Michigan–Ann ArborJoseph J. Park - University of Michigan–Ann ArborAjjai Alva - University of Michigan–Ann ArborRana 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
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.clgc.2024.102198
- ISSN
- 1558-7673
- eISSN
- 1938-0682
- 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
- 08/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984696783502771
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