scholarly journals Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?

Author(s):  
Anne Zaremba ◽  
Eleftheria Chorti ◽  
Finja Jockenhöfer ◽  
Saskia Bolz ◽  
Selma Sirin ◽  
...  
2020 ◽  
Vol 16 (31) ◽  
pp. 2521-2536
Author(s):  
Sunandana Chandra ◽  
Ying Zheng ◽  
Shivani Pandya ◽  
Ting Yu ◽  
Mairead Kearney ◽  
...  

Aim: Retrospectively assessed treatment patterns and clinical and economic outcomes in Merkel cell carcinoma (MCC) patients receiving recommended first-line regimens. Materials & methods: MCC patients newly treated with either immune checkpoint inhibitors (ICIs) or chemotherapies (CTs) were selected from the Veterans Health Administration database (2013–2018); 74 patients (ICIs: 20 and CTs: 54) were selected. Results: Median duration of therapy was 300 days for ICIs and 91 days for CTs. Time to next treatment was 245 and 184 days, respectively. Mean total (per patient per month) costs were $15,306 (ICIs) and $10,957 (CTs), of which 51% and 86%, respectively, were non-MCC therapy-related costs. Conclusion: Despite higher costs, utilization of ICIs in first-line MCC shows clinical advantages over CTs in the real world.


2020 ◽  
Vol 2 (11) ◽  
pp. 2202-2207 ◽  
Author(s):  
H. M. Stege ◽  
F. Bradfisch ◽  
M. I. Fleischer ◽  
P. Mohr ◽  
S. Ugurel ◽  
...  

AbstractSignificant progress has been made in the treatment of advanced Merkel cell carcinoma (MCC) by establishing immune checkpoint inhibitors (ICI). Tumor progression, durable response, or adverse events may lead to ICI discontinuation in MCC patients. If in these patients tumor progression occurs, the question remains if re-induction with ICI achieves renewed tumor response. This retrospective multicenter study evaluated patients in with re-induction of anti-PD-1/anti-PD-L1 therapy for advanced MCC. Clinical data were extracted at treatment initiation, tumor response, treatment cessation, and subsequent tumor response to re-induction. Eight patients from seven centers (mean age 67.8 years) were included. The median duration of initial therapy with anti-PD-1/anti-PD-L1 was 9.6 months (2–21 months). Two patients achieved complete response (CR), four patients partial response (PR), one patient stable disease (SD), while in one patient progressive disease (PD) occurred as best overall response (BOR) to ICI. Reason for discontinuation of ICI was PD in three patients and severe adverse events in five patients. Following a median anti-PD-1/anti-PD-L1 therapy-free interval of 9.5 months (3–18 months), re-induction with ICI therapy was initiated. Five of eight patients (62.5%) achieved an objective response upon re-induction, while in three patients, no response could be observed. Notably, adverse events, which had led to the discontinuation of the first ICI treatment line, were not observed upon re-induction. The initial response to immune checkpoint inhibitors seems to be an important marker for successful re-induction. Interestingly, adverse events leading to treatment discontinuation were not observed during re-induction.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 718
Author(s):  
Elena Dellambra ◽  
Maria Luigia Carbone ◽  
Francesca Ricci ◽  
Francesco Ricci ◽  
Francesca Romana Di Pietro ◽  
...  

Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease. 


2019 ◽  
Vol 9 (1) ◽  
pp. 53-58
Author(s):  
K. V. Orlova ◽  
V. V. Nazarova ◽  
N. N. Petenko ◽  
L. V. Demidov

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with limited treatment options in later stages, when the mortality rate due to the disease is as high as 46 %. It has been demonstrated earlier that MCC is an immunogenic tumor, therefore the emergence of immune checkpoint inhibitors has changed the treatment principles for patients with advanced MCC. In this article, we present the initial results of the use of avelumab, an anti‑PD–L1 antibody, in the treatment of patients with metastatic and/or locally advanced MCC as part of the early access program in Russia.


2020 ◽  
Vol 8 (2) ◽  
pp. e000700
Author(s):  
Alison M Weppler ◽  
Andrew Pattison ◽  
Prachi Bhave ◽  
Paolo De Ieso ◽  
Jeanette Raleigh ◽  
...  

BackgroundMetastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials.MethodsMedical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed.Results23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1–2 immune-related adverse events.ConclusionICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.


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