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Avelumab Induced Severe Disabling Myositis in A Patient with Merkel Cell Carcinoma

Author(s): Georg Lodde, Lisa Zimmer, Elisabeth Livingstone, Christina Drusio, Sarah Knispel, Eva Hadaschik, Axel Wetter, Jürgen C. Becker, Dirk Schadendorf, Selma Ugurel

Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with a poor survival rate. Nearly 30% of MCC patients develop metastatic disease. Until recently, patients with inoperable metastasised Merkel cell carcinoma had an extremely poor prognosis with a median overall survival of far below 12 months. After the introduction of immune checkpoint blockade it became obvious that the anti-PD-1/PD-L1 inhibitors pembrolizumab, nivolumab and avelumab are highly efficacious in MCC with durable responses in 20-40% of patients leading to a significant prolongation of survival times. PD-1/PD-L1 blockers are generally well tolerated. In the following we report a patient with advanced metastatic MCC who responded to avelumab but developed a severe, disabling therapy-induced myositis which did not resolve after therapy discontinuation. This is the first report on a severe myositis caused by avelumab leaving the patient to be permanently wheelchair-bound.

Case Presentation: An 85 year-old male presented with multiple cutaneous and subcutaneous nodes of the left leg and groin. The patient’s history revealed diagnosis of MCC of the left buttock and synchronous macroscopic lymph node metastasis of the left groin 4 years ago, treated with complete lymphadenectomy followed by adjuvant radiation of all tumor sites. Staging showed an advanced metastatic MCC. Treatment with avevulamb was started. Re-staging 3 months after start of avelumab showed a partial response. The patient developed a therapy-induced myositis despite a corticosteroid support of methylprednisolone, an additional immuno-suppressive treatment with infliximab and discontinuation of treatment. 8 months after start of avelumab the patient is in stable disease. However, the severe weakness of both legs has not resolved and the patient remains immobilized and wheelchair-bound.

Conclusion: In 2017, MCC was the first cancer entity for which avelumab gained approval. Thus, data on the toxicity profile of this drug are not as mature as data on other checkpoint inhibitors. Due to the high efficacy of this class of drugs, the lack of alternative therapeutic strategies and the limited experience of long-term outcome of patients discontinuing treatment, the decision to stop anti-PD-1/PD-L1 treatment in patients developing toxicities is difficult.

 

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