Extremely Long Survival under Combined Immunotherapy in a Metastatic Functional Neuroendocrine Neoplasia Patient

Schmidt, Daniel; Wiedenmann, Bertram

doi:10.1159/000486417

Cited by 13 publications

(10 citation statements)

References 31 publications

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“…Further work might appreciate the transformation in proliferation during the period of treatment. As also observed in another case report of immunotherapy in neuroendocrine tumors, the proliferation index decreased during therapy [42]. This could be a working point for future evaluation of the tumor grading, leading to therapeutic adaptation or potential new treatment options.…”

Section: Discussionsupporting

confidence: 63%

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Sustained partial remission of a metastatic NEN using off-label immunotherapy with pembrolizumab

Stüven

Wiedenmann

2019

Oncotarget

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Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumors, which can be histologically separated by primary location, proliferation rate and differentiation of tumor cells. The therapeutic options and outcome depend on grading, staging and resectability of the tumor. Established treatment options of neuroendocrine tumors (NET) and carcinomas (NEC) are based especially on surgery, tumor specific medical treatments, peptide guided radioreceptor therapy (PRRT) and locoregional therapies. We report about a patient diagnosed with a pancreatic, non-functional NET/NEC G2/3 with a proliferation rate of 20% at initial immunohistochemical diagnosis. During the course of the disease, the proliferation rate increased up to more than 50% over a period of 5 years. Due to loss of response to established therapies (i.e. systemic chemotherapy, targeted therapy and brachytherapy), an off-label immunotherapy with the PD-1 antibody pembrolizumab was initiated based on a 30% PD-L1 expression in tumor cells. This report is the first demonstrating a partial remission of a pancreatic NEN using pembrolizumab monotherapy with a hepatic tumor volume reduction of at least 66%, combined with an improvement of the Karnofsky score rising from 60% to 100%. This case offers insight into the potential role of immunotherapy in a subgroup of neuroendocrine neoplasms.

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Section: Discussionsupporting

confidence: 63%

“…Furthermore, since we have already successfully treated another patient with pembrolizumab and ipilimumab long term [42], based on a high mutational burden, it is tempting to speculate that long-term remission may also be observed in the presented patient with elevated PD-L1 expression as a predictive marker for therapeutic response.…”

Section: Discussionmentioning

confidence: 99%

Sustained partial remission of a metastatic NEN using off-label immunotherapy with pembrolizumab

Stüven

Wiedenmann

2019

Oncotarget

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“…Another case report by Schmidt et al, 24 type III metastatic gastric NEN who had high TMB. However, this patient had significant therapeutic response with a long survival of 8 years, although it was not clear whether the prolonged benefit was from the chemotherapy or immunotherapy.…”

Section: Initial Trials Of Icpis In Gep-mentioning

confidence: 95%

Role of immunotherapy in gastro‐enteropancreatic neuroendocrine neoplasms (gep‐nens): Current advances and future directions

Liu

Dasari

Dowlati

et al. 2021

J Neuroendocrinology

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The role of the immune system in cancer treatment was first described in the late 19th Century when Dr William Coley observed that injecting killed bacteria into sarcoma led to tumour shrinkage. 1-5 In the past few decades, significant advances have been made in the understanding of the intersection between immune surveillance and tumour growth. It is because of this that immune-mediated therapeutic advances have occurred more recently. The gastroenteropancreatic (GEP)-neuroendocrine neoplasms (NEN) tumour microenvironment is enriched with immune cells that include natural killer cells, immunosuppressive regulatory T cells, tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages. From this, various therapeutic approaches are being studied to unleash the immune system and control the growth of NENs. 6 One approach in particular uses check point inhibitors of the programmed cell

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“…Intensive multimodal treatment which included combined vaccination and PD-1/CTLA-4 blockade led to extremely long survival of more than 8 years with high quality of life and minimal residual disease in a patient with a histamine-secreting metastasized type 3 gastric NET, despite dedifferentiation of the tumor into a non-functional NEC [53]. …”

Section: Clinical Experience With Checkpoint Inhibitors In Nensmentioning

confidence: 99%

Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia

Weber

Fottner²

2018

Oncol Res Treat

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Background: Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. Method: Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs. Results: Evidence points to an important role of immune phenomena in the pathogenesis and treatment of neuroendocrine tumors (NETs). Programmed cell death 1 (PD-1) protein and its ligand are mainly expressed in poorly differentiated NENs. Microsatellite instability and high mutational load are more pronounced in high-grade NENs and may predict response to immunotherapy. Clinical experience of immune checkpoint blockade mainly exists for Merkel cell carcinoma, a high-grade cutaneous neuroendocrine carcinoma (NEC), which has led to approval of the anti-PD-1 antibody avelumab. In addition, there is anecdotal evidence for the efficacy of checkpoint inhibitors in large-cell lung NECs, ovarian NECs and others, including gastroenteropancreatic NENs. Currently, phase II studies investigate PDR001, pembrolizumab, combined durvalumab and tremelimumab, and avelumab treatment in patients with advanced/metastatic NENs. Conclusion: Immune checkpoint inhibitors are a promising therapeutic option, especially in progressive NECs or high-grade NETs with high tumor burden, microsatellite instability, and/or mutational load.

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Extremely Long Survival under Combined Immunotherapy in a Metastatic Functional Neuroendocrine Neoplasia Patient

Cited by 13 publications

References 31 publications

Sustained partial remission of a metastatic NEN using off-label immunotherapy with pembrolizumab

Sustained partial remission of a metastatic NEN using off-label immunotherapy with pembrolizumab

Role of immunotherapy in gastro‐enteropancreatic neuroendocrine neoplasms (gep‐nens): Current advances and future directions

Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia

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