Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series

J R Platt; J Allotey; E Alouani; J Glasbey; R Intini; S Lonardi; G Mazzoli; A M Militello; D P Modest; J Palle; F Pietrantonio; K Riyad; L Samuel; A V Schulze; K K Shiu; J Taieb; D J M Tolan; N P West; A C Westwood; C J M Williams; J F Seligmann

doi:10.1016/j.esmoop.2024.103698

Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series

J R Platt^* (Corresponding Author), J Allotey, E Alouani, J Glasbey, R Intini, S Lonardi, G Mazzoli, A M Militello, D P Modest, J Palle, F Pietrantonio, K Riyad, L Samuel, A V Schulze, K K Shiu, J Taieb, D J M Tolan, N P West, A C Westwood, C J M WilliamsJ F Seligmann

^*Corresponding author for this work

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Abstract

BACKGROUND: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.

PATIENTS AND METHODS: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified. Data on patient, disease, treatment, and response-specific factors were explored for potential risk factors. Overall treatment numbers were used to estimate incidence.

RESULTS: Nine patients from eight European centres were included. Common features were hepatic flexure location (5/9), T4 radiological staging (6/9), annular shape (8/9), radiological stricturing (5/9), and endoscopic obstruction (6/9). All received pembrolizumab and obstructed between 45 and 652 days after starting treatment. Seven patients underwent surgical resection; one was managed with a defunctioning stoma; and one was managed conservatively. One patient died from obstruction. Radiological response was seen in eight patients, including two complete responses. Pathological response was seen in all seven who underwent resection, including four complete responses. The overall incidence of immunotherapy response-related obstruction in these centres was 1.51%.

CONCLUSIONS: Bowel obstruction associated with immunotherapy response may represent a rare treatment-related complication in dMMR CC. Clinicians must recognise this safety signal and share experience to maintain patient safety.

Original language	English
Article number	103698
Number of pages	7
Journal	ESMO Open
Volume	9
Issue number	9
Early online date	5 Sept 2024
DOIs	https://doi.org/10.1016/j.esmoop.2024.103698
Publication status	Published - Sept 2024

Bibliographical note

All contributors to this manuscript are listed as authors.

Funding

This work was supported by a Cancer Research UK Clinical Research Training Fellowship (award reference S4154 to ACW); Cancer Research UK [grant number RCCCTF-Nov21/100001 to CJMW]; and Yorkshire Cancer Research [grant number L394 to DJMT and NPW].

Funders	Funder number
Cancer Research UK	RCCCTF-Nov21/100001
Yorkshire Cancer Research	L394

Keywords

colon cancer
immunotherapy
regression
bowel obstruction
case series

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Platt, J. R., Allotey, J., Alouani, E., Glasbey, J., Intini, R., Lonardi, S., Mazzoli, G., Militello, A. M., Modest, D. P., Palle, J., Pietrantonio, F., Riyad, K., Samuel, L., Schulze, A. V., Shiu, K. K., Taieb, J., Tolan, D. J. M., West, N. P., Westwood, A. C., ... Seligmann, J. F. (2024). Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series. ESMO Open, 9(9), Article 103698. https://doi.org/10.1016/j.esmoop.2024.103698

Platt, JR, Allotey, J, Alouani, E, Glasbey, J, Intini, R, Lonardi, S, Mazzoli, G, Militello, AM, Modest, DP, Palle, J, Pietrantonio, F, Riyad, K, Samuel, L, Schulze, AV, Shiu, KK, Taieb, J, Tolan, DJM, West, NP, Westwood, AC, Williams, CJM & Seligmann, JF 2024, 'Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series', ESMO Open, vol. 9, no. 9, 103698. https://doi.org/10.1016/j.esmoop.2024.103698

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abstract = "BACKGROUND: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.PATIENTS AND METHODS: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified. Data on patient, disease, treatment, and response-specific factors were explored for potential risk factors. Overall treatment numbers were used to estimate incidence.RESULTS: Nine patients from eight European centres were included. Common features were hepatic flexure location (5/9), T4 radiological staging (6/9), annular shape (8/9), radiological stricturing (5/9), and endoscopic obstruction (6/9). All received pembrolizumab and obstructed between 45 and 652 days after starting treatment. Seven patients underwent surgical resection; one was managed with a defunctioning stoma; and one was managed conservatively. One patient died from obstruction. Radiological response was seen in eight patients, including two complete responses. Pathological response was seen in all seven who underwent resection, including four complete responses. The overall incidence of immunotherapy response-related obstruction in these centres was 1.51%.CONCLUSIONS: Bowel obstruction associated with immunotherapy response may represent a rare treatment-related complication in dMMR CC. Clinicians must recognise this safety signal and share experience to maintain patient safety.",

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author = "Platt, {J R} and J Allotey and E Alouani and J Glasbey and R Intini and S Lonardi and G Mazzoli and Militello, {A M} and Modest, {D P} and J Palle and F Pietrantonio and K Riyad and L Samuel and Schulze, {A V} and Shiu, {K K} and J Taieb and Tolan, {D J M} and West, {N P} and Westwood, {A C} and Williams, {C J M} and Seligmann, {J F}",

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AU - Platt, J R

AU - Allotey, J

AU - Alouani, E

AU - Glasbey, J

AU - Intini, R

AU - Lonardi, S

AU - Mazzoli, G

AU - Militello, A M

AU - Modest, D P

AU - Palle, J

AU - Pietrantonio, F

AU - Riyad, K

AU - Samuel, L

AU - Schulze, A V

AU - Shiu, K K

AU - Taieb, J

AU - Tolan, D J M

AU - West, N P

AU - Westwood, A C

AU - Williams, C J M

AU - Seligmann, J F

N1 - All contributors to this manuscript are listed as authors.

PY - 2024/9

Y1 - 2024/9

N2 - BACKGROUND: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.PATIENTS AND METHODS: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified. Data on patient, disease, treatment, and response-specific factors were explored for potential risk factors. Overall treatment numbers were used to estimate incidence.RESULTS: Nine patients from eight European centres were included. Common features were hepatic flexure location (5/9), T4 radiological staging (6/9), annular shape (8/9), radiological stricturing (5/9), and endoscopic obstruction (6/9). All received pembrolizumab and obstructed between 45 and 652 days after starting treatment. Seven patients underwent surgical resection; one was managed with a defunctioning stoma; and one was managed conservatively. One patient died from obstruction. Radiological response was seen in eight patients, including two complete responses. Pathological response was seen in all seven who underwent resection, including four complete responses. The overall incidence of immunotherapy response-related obstruction in these centres was 1.51%.CONCLUSIONS: Bowel obstruction associated with immunotherapy response may represent a rare treatment-related complication in dMMR CC. Clinicians must recognise this safety signal and share experience to maintain patient safety.

AB - BACKGROUND: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.PATIENTS AND METHODS: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified. Data on patient, disease, treatment, and response-specific factors were explored for potential risk factors. Overall treatment numbers were used to estimate incidence.RESULTS: Nine patients from eight European centres were included. Common features were hepatic flexure location (5/9), T4 radiological staging (6/9), annular shape (8/9), radiological stricturing (5/9), and endoscopic obstruction (6/9). All received pembrolizumab and obstructed between 45 and 652 days after starting treatment. Seven patients underwent surgical resection; one was managed with a defunctioning stoma; and one was managed conservatively. One patient died from obstruction. Radiological response was seen in eight patients, including two complete responses. Pathological response was seen in all seven who underwent resection, including four complete responses. The overall incidence of immunotherapy response-related obstruction in these centres was 1.51%.CONCLUSIONS: Bowel obstruction associated with immunotherapy response may represent a rare treatment-related complication in dMMR CC. Clinicians must recognise this safety signal and share experience to maintain patient safety.

KW - colon cancer

KW - immunotherapy

KW - regression

KW - bowel obstruction

KW - case series

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DO - 10.1016/j.esmoop.2024.103698

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SN - 2059-7029

VL - 9

JO - ESMO Open

JF - ESMO Open

IS - 9

M1 - 103698

ER -

Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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