Caring for Patients Treated With Checkpoint Inhibitors for the Treatment of Metastatic Merkel Cell Carcinoma

2019 ◽  
Vol 35 (5) ◽  
pp. 150924
Author(s):  
Krista M. Rubin ◽  
Brianna Hoffner ◽  
Andrea Carroll Bullock
2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Sophia Z. Shalhout ◽  
Kevin S. Emerick ◽  
Peter M. Sadow ◽  
Jenny J. Linnoila ◽  
David M. Miller

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer with a high risk of recurrence and metastasis. MCC is generally associated with advanced age, fair skin, sun exposure, immunosuppression, and in the majority of cases, the Merkel cell polyomavirus. Neuroendocrine malignancies are associated with a variety of paraneoplastic neurological syndromes (PNS), characterized as autoimmune responses to malignancy-associated expression of neural antigens. Our literature review underscores previous case reports of MCC-associated PNS with voltage-gated calcium channel (VGCC) and anti-Hu (or ANNA-1) autoantibodies. We present the case of a 59-year-old male with regionally metastatic Merkel cell carcinoma complicated by the paraneoplastic manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. His primary lower neck subcutaneous MCC and metastasis were initially treated with surgery. Additional recurrent lymph node metastases were successfully treated with definitive intensity-modulated radiation therapy. His PNS improved with rituximab therapy. Although rare, this case highlights that in the setting of seizures and prominent psychiatric symptoms accompanying an MCC diagnosis, evaluation for autoimmune paraneoplastic encephalitis is warranted. Awareness and detection of preexisting PNS are crucial in the era of immune checkpoint inhibitors (ICI) for advanced MCC, where treatment with ICI has the potential to exacerbate preexisting autoimmune PNS and lead to worsened or even lethal neurologic immune-related adverse events (nirAEs).


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15696-e15696
Author(s):  
Aman Chauhan ◽  
Leaundra Murray ◽  
Arun Kumar Arumugam Raajasekar ◽  
Zin Myint ◽  
Lowell Brian Anthony

e15696 Background: Neuroendocrine tumor of unknown primary constitutes about 10-15 % of all neuroendocrine tumors. Identification of primary site can helps alter the management. Sunitinib is FDA approved for management of pancreatic neuroendocrine tumors, everolimus is approved for gastroenteropancreatic and bronchial NETs, immune checkpoint inhibitors are active in Merkel cell carcinoma and MIBG treatment is standard of care for pheochromocytoma. Methods: Patients with neuroendocrine tumor with unknown primary were identified from Markey Cancer Center database over a five-year period (2012-2016). Patient who underwent 92-gene reverse transcriptase polymerase chain reaction cancer classification assay (BioTheranostics Tissue Type ID) were analyzed. IRB approval was obtained. Results: 56 patients with neuroendocrine tumors with unknown primary were identified. Median age of cohort was 61 years. 28/56 patients were males. 92 gene cancer ID assay was used in 38 out of 56 patients. Primary site of tumor was identified with > 95% certainty in 36 out of 38 patients. The test reported pancreatic NET as the primary site for 10 patients, gastrointestinal NETs for 14 patients, bronchial carcinoid for 5, large call NEC for 3, Merkel cell carcinoma for two and pheochromocytoma in one patient. Conclusions: Tissue type ID was able to identify a primary site in NETs of unknown primary in majority (94.7%) of cases. The result had direct implication in management of patients with regards to FDA approved treatment options in 13/38 patients (pNETs, merkel cell and pheochromocytoma).


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14098-e14098
Author(s):  
Theresa N Canavan ◽  
Nicole Adell Doudican ◽  
Mary Stevenson ◽  
Anna C. Pavlick ◽  
John Carucci

e14098 Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin that is highly immunogenic. Checkpoint inhibitors (CPI) have recently revolutionized the treatment of advanced MCC. In this study we sought to better understand how CPI are used in an outpatient setting and to better define MCC outcomes associated with their use. Methods: We conducted a retrospective chart review of MCC patients seen in the New York University Hematology and Oncology Department from 2012-2018. Patient characteristics and treatment regimens were compared between those with and without disease progression at any point during follow-up. Results: Fifteen patients were identified, 46.7% of whom presented with nodal or distant disease (Table). Nine patients experienced relapse during follow-up. There were no MCC-specific deaths, and 92.3% of patients were without evidence of MCC at the end of follow-up. Ten patients were treated with one or more CPI (pembrolizumab, nivolumab, ipilimumab) either in the setting of first line systemic therapy (71.4%) or after experiencing disease progression (28.6%). There was a trend toward improved relapse free survival with CPI use (P = 0.054). Conclusions: Although recurrences were common, overall outcomes at the end of follow-up were very good. CPI were well tolerated and were associated with a trend toward improved relapse free survival. Patients with advanced stage MCC would benefit from consideration of CPI as part of their treatment options. [Table: see text]


2020 ◽  
Vol 140 (7) ◽  
pp. S63
Author(s):  
M. Babadzhanov ◽  
N. Doudican ◽  
C. Ovits ◽  
T. Canavan ◽  
M. Stevenson ◽  
...  

2020 ◽  
Vol 13 (2) ◽  
pp. 501-507
Author(s):  
Ana Monteiro ◽  
Emanuel Gouveia ◽  
Daniela Garcez ◽  
Sara Donato ◽  
Diogo Martins-Branco ◽  
...  

Merkel cell carcinoma is a rare and aggressive cutaneous tumor, and the use of checkpoint inhibitors immunotherapy is a recent indication in its metastatic setting, both first and second line. However, the widespread use of immunotherapy is associated with an increase of acute and late immune-mediated adverse events. We present a case of an elderly fit patient with metastatic Merkel cell carcinoma treated with pembrolizumab who developed diabetic ketoacidosis, a severe immune-mediated adverse event. A multidisciplinary approach was crucial to overcome the life-threatening event. Even with early treatment stop, the patient had a significant and durable response to the treatment for 15 months. Meanwhile, a progressive pan-cerebellar syndrome emerged, possible due to a paraneoplastic syndrome with a negative onco-neuronal antibody panel, although an autoimmune etiology associated with immunotherapy could not be excluded. Unfortunately, the situation was irreversible and refractory to immunomodulatory treatment. Despite the unpredictable toxicity, it is important to note the efficacy profile, with a progression-free survival of 15 months, which is higher than the one reported in reference clinical trials in this setting.


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 12 (2) ◽  
pp. 639-643 ◽  
Author(s):  
Sandy Tun Min ◽  
Ina I.C. Nordman ◽  
Huy A. Tran

Merkel cell carcinoma is a rare but aggressive skin cancer. Response to chemotherapy is not durable but avelumab, an anti-PD-L1 inhibitor, showed promising ongoing response in a phase II trial. Checkpoint inhibitors including avelumab are known to cause overactivation of the immune system, leading to immune-related adverse events (irAE). We describe the first reported case of hypercalcaemia secondary to reactivation of sarcoidosis in a patient with metastatic Merkel cell carcinoma on avelumab. Hypercalcaemia was managed with corticosteroids to full resolution and avelumab therapy was safely continued.


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