Abstract
Background
Immune-Checkpoint-inhibitors (ICIs) are approved in first line therapy of microsatellite-instable,
deficient miss-match-repair (MSI-H-dMMR) metastatic colorectal cancer (mCRC), and
in second line after standard chemotherapy. Evidence supporting immunotherapy after
immunotherapy is scarce.
Case report
This case report highlights the course of a heavily pretreated patient with MSI-H
mCRC with progression after multiple local therapies, standard chemotherapies and
pembrolizumab. After 4 cycles of ipilimumab and nivolumab followed by nivolumab-maintenance
he achieved a long-lasting disease control of 22 months. After further subsequent
progression he regained immune mediated disease control by a second “boost” of ipilimumab.
Conclusion
Re-exposition with ipilimumab is a potential option to restore immune-mediated-disease-control
in patients with preceding long-lasting response to ipilimumab/nivolumab and with
dMMR-tumors. The clinical situation of progress after long-lasting disease control
on ICIs becomes more common and is an opportunity to investigate potential strategies
for restoring immune mediated disease control.
Keywords
List of Abbreviations:
mCRC (metastatic colorectal cancers), ICIs (Immune-Checkpoint Inhibitors), MSI-H (microsatellite instable high), dMMR (deficient mismatch repair)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Colorectal CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Deficient mismatch repair system in patients with sporadic advanced colorectal cancer.Br J Cancer. 2009; 100: 266-273https://doi.org/10.1038/sj.bjc.6604867
- Microsatellite instability is associated with the presence of lynch syndrome pan-cancer.J Clin Oncol. 2019; 37: 286-295https://doi.org/10.1200/JCO.18.00283
- Pembrolizumab in microsatellite-instability-high advanced colorectal cancer.N Engl J Med. 2020; 383: 2207-2218https://doi.org/10.1056/NEJMoa2017699
- Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: KEYNOTE-164.J Clin Oncol. 2020; 38: 11-19https://doi.org/10.1200/JCO.19.02107
- Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.Lancet Oncol. 2017; 18: 1182-1191https://doi.org/10.1016/S1470-2045(17)30422-9
- Durable clinical benefit with nivolumab plus Ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer.J Clin Oncol. 2018; 36: 773-779https://doi.org/10.1200/JCO.2017.76.9901
- Immunotherapy after immunotherapy: response rescue in a patient with microsatellite instability-high colorectal cancer post-Pembrolizumab.Clin Colorectal Cancer. 2020; 19: 137-140https://doi.org/10.1016/j.clcc.2020.02.006
- Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer.J Clin Oncol. 2010; 28: 3485-3490https://doi.org/10.1200/JCO.2010.28.3994
- Treatment after progression in the era of immunotherapy.Lancet Oncol. 2020; 21: e463-e476https://doi.org/10.1016/S1470-2045(20)30328-4
- Loss of PTEN promotes resistance to T cell-mediated immunotherapy.Cancer Discov. 2016; 6: 202-216https://doi.org/10.1158/2159-8290.CD-15-0283
- Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity.Nature. 2015; 523: 231-235https://doi.org/10.1038/nature14404
- Ipilimumab with anti PD-1 (nivovlumab or pembrolizumab) after progression on first line anti-PD-1 therapy for advanced melanoma.J Clin Oncol. 2018; 36 (e21552–e21552)
- Phase II trial of pembrolizumab (pembro) plus 1 mg/kg ipilimumab (ipi) immediately following progression on anti-PD-1 Ab in melanoma (mel).J Clin Oncol. 2018; 36 (9514–9514)
- Efficacy and safety of retreatment with ipilimumab in patients with pretreated advanced melanoma who progressed after initially achieving disease control.Clin Cancer Res. 2013; 19: 2232-2239https://doi.org/10.1158/1078-0432.CCR-12-3080
- Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies.Ann Oncol. 2014; 25: 2277-2284https://doi.org/10.1093/annonc/mdu441
- Ipilimumab retreatment in patients with pretreated advanced melanoma: the expanded access programme in Italy.Br J Cancer. 2014; 110: 1721-1726https://doi.org/10.1038/bjc.2014.126
Article Info
Publication History
Published online: January 07, 2022
Accepted:
January 3,
2022
Received in revised form:
December 26,
2021
Received:
May 24,
2021
Footnotes
Editor: Dr E CCHU
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
