The value of MMR characterization and efficacy of checkpoint inhibitor in patients with small-bowel adenocarcinomas: a retrospective real-world cohort study

Rasmus Haunstrup Døssing; Julia johanna Almer Bromann; Karina Seierøe; Estrid Vilma Solyom Høgdall; Tim Svenstrup Poulsen; Jakob Hagen Vasehus Schou; Dan Taksony Solyom Hoegdall

doi:10.1016/j.esmorc.2025.100030

The value of MMR characterization and efficacy of checkpoint inhibitor in patients with small-bowel adenocarcinomas: a retrospective real-world cohort study

Rasmus Haunstrup Døssing, Julia johanna Almer Bromann, Karina Seierøe, Estrid Vilma Solyom Høgdall, Tim Svenstrup Poulsen, Jakob Hagen Vasehus Schou, Dan Taksony Solyom Hoegdall

Abstract

Background
Small-bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with a poor prognosis and limited treatment options. Given its rarity, clinical management often mirrors colorectal cancer (CRC), despite distinct molecular features and inferior outcomes. Although checkpoint inhibitor (CPI) therapy has shown efficacy in mismatch repair-deficient (dMMR) CRC, data on SBA remain scarce, and MMR testing is not routinely implemented.
Patients and methods
We conducted a retrospective study of SBA patients treated with CPI at Copenhagen University Hospital—Herlev between March 2019 and January 2024. Radiological responses were assessed using RECIST v1.1. We also analyzed the frequency of MMR testing and dMMR status in SBA patients.
Results
Among 148 SBA patients, 7 received CPI therapy. The objective response rate was 86%, with one (14%) complete response and five (71%) partial responses. Median progression-free survival was 31 months [median follow-up (mFU) 32 months]; median overall survival was not reached (mFU 33 months). Overall, 55% underwent MMR testing, and 18% of SBA patients were dMMR.
Conclusions
CPI therapy yields high, durable response rates in dMMR SBA, supporting dMMR as a predictive biomarker. However, inconsistent MMR testing strategy may limit access to optimal treatment. Routine molecular profiling and broader biomarker discovery are key to expanding CPI eligibility and improving outcomes.

Originalsprog	Engelsk
Artikelnummer	100030
Tidsskrift	ESMO Rare Cancers
Vol/bind	4
Udgave nummer	C
ISSN	3050-4619
DOI	https://doi.org/10.1016/j.esmorc.2025.100030
Status	Udgivet - 2025

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10.1016/j.esmorc.2025.100030Licens: CC BY

Citationsformater

Døssing, R. H., Bromann, J. J. A., Seierøe, K., Høgdall, E. V. S., Poulsen, T. S., Schou, J. H. V., & Hoegdall, D. T. S. (2025). The value of MMR characterization and efficacy of checkpoint inhibitor in patients with small-bowel adenocarcinomas: a retrospective real-world cohort study. ESMO Rare Cancers, 4(C), Artikel 100030. https://doi.org/10.1016/j.esmorc.2025.100030

The value of MMR characterization and efficacy of checkpoint inhibitor in patients with small-bowel adenocarcinomas: a retrospective real-world cohort study. / Døssing, Rasmus Haunstrup ; Bromann, Julia johanna Almer; Seierøe, Karina et al.
I: ESMO Rare Cancers, Bind 4, Nr. C, 100030, 2025.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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title = "The value of MMR characterization and efficacy of checkpoint inhibitor in patients with small-bowel adenocarcinomas: a retrospective real-world cohort study",

abstract = "BackgroundSmall-bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with a poor prognosis and limited treatment options. Given its rarity, clinical management often mirrors colorectal cancer (CRC), despite distinct molecular features and inferior outcomes. Although checkpoint inhibitor (CPI) therapy has shown efficacy in mismatch repair-deficient (dMMR) CRC, data on SBA remain scarce, and MMR testing is not routinely implemented.Patients and methodsWe conducted a retrospective study of SBA patients treated with CPI at Copenhagen University Hospital—Herlev between March 2019 and January 2024. Radiological responses were assessed using RECIST v1.1. We also analyzed the frequency of MMR testing and dMMR status in SBA patients.ResultsAmong 148 SBA patients, 7 received CPI therapy. The objective response rate was 86%, with one (14%) complete response and five (71%) partial responses. Median progression-free survival was 31 months [median follow-up (mFU) 32 months]; median overall survival was not reached (mFU 33 months). Overall, 55% underwent MMR testing, and 18% of SBA patients were dMMR.ConclusionsCPI therapy yields high, durable response rates in dMMR SBA, supporting dMMR as a predictive biomarker. However, inconsistent MMR testing strategy may limit access to optimal treatment. Routine molecular profiling and broader biomarker discovery are key to expanding CPI eligibility and improving outcomes.",

author = "D{\o}ssing, {Rasmus Haunstrup} and Bromann, {Julia johanna Almer} and Karina Seier{\o}e and H{\o}gdall, {Estrid Vilma Solyom} and Poulsen, {Tim Svenstrup} and Schou, {Jakob Hagen Vasehus} and Hoegdall, {Dan Taksony Solyom}",

year = "2025",

doi = "10.1016/j.esmorc.2025.100030",

language = "English",

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journal = "ESMO Rare Cancers",

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T1 - The value of MMR characterization and efficacy of checkpoint inhibitor in patients with small-bowel adenocarcinomas

T2 - a retrospective real-world cohort study

AU - Døssing, Rasmus Haunstrup

AU - Bromann, Julia johanna Almer

AU - Seierøe, Karina

AU - Høgdall, Estrid Vilma Solyom

AU - Poulsen, Tim Svenstrup

AU - Schou, Jakob Hagen Vasehus

AU - Hoegdall, Dan Taksony Solyom

PY - 2025

Y1 - 2025

N2 - BackgroundSmall-bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with a poor prognosis and limited treatment options. Given its rarity, clinical management often mirrors colorectal cancer (CRC), despite distinct molecular features and inferior outcomes. Although checkpoint inhibitor (CPI) therapy has shown efficacy in mismatch repair-deficient (dMMR) CRC, data on SBA remain scarce, and MMR testing is not routinely implemented.Patients and methodsWe conducted a retrospective study of SBA patients treated with CPI at Copenhagen University Hospital—Herlev between March 2019 and January 2024. Radiological responses were assessed using RECIST v1.1. We also analyzed the frequency of MMR testing and dMMR status in SBA patients.ResultsAmong 148 SBA patients, 7 received CPI therapy. The objective response rate was 86%, with one (14%) complete response and five (71%) partial responses. Median progression-free survival was 31 months [median follow-up (mFU) 32 months]; median overall survival was not reached (mFU 33 months). Overall, 55% underwent MMR testing, and 18% of SBA patients were dMMR.ConclusionsCPI therapy yields high, durable response rates in dMMR SBA, supporting dMMR as a predictive biomarker. However, inconsistent MMR testing strategy may limit access to optimal treatment. Routine molecular profiling and broader biomarker discovery are key to expanding CPI eligibility and improving outcomes.

AB - BackgroundSmall-bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with a poor prognosis and limited treatment options. Given its rarity, clinical management often mirrors colorectal cancer (CRC), despite distinct molecular features and inferior outcomes. Although checkpoint inhibitor (CPI) therapy has shown efficacy in mismatch repair-deficient (dMMR) CRC, data on SBA remain scarce, and MMR testing is not routinely implemented.Patients and methodsWe conducted a retrospective study of SBA patients treated with CPI at Copenhagen University Hospital—Herlev between March 2019 and January 2024. Radiological responses were assessed using RECIST v1.1. We also analyzed the frequency of MMR testing and dMMR status in SBA patients.ResultsAmong 148 SBA patients, 7 received CPI therapy. The objective response rate was 86%, with one (14%) complete response and five (71%) partial responses. Median progression-free survival was 31 months [median follow-up (mFU) 32 months]; median overall survival was not reached (mFU 33 months). Overall, 55% underwent MMR testing, and 18% of SBA patients were dMMR.ConclusionsCPI therapy yields high, durable response rates in dMMR SBA, supporting dMMR as a predictive biomarker. However, inconsistent MMR testing strategy may limit access to optimal treatment. Routine molecular profiling and broader biomarker discovery are key to expanding CPI eligibility and improving outcomes.

U2 - 10.1016/j.esmorc.2025.100030

DO - 10.1016/j.esmorc.2025.100030

M3 - Journal article

SN - 3050-4619

VL - 4

JO - ESMO Rare Cancers

JF - ESMO Rare Cancers

IS - C

M1 - 100030

ER -

The value of MMR characterization and efficacy of checkpoint inhibitor in patients with small-bowel adenocarcinomas: a retrospective real-world cohort study

Abstract

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