Hypercalcaemia due to Sarcoidosis during Treatment with Avelumab for Metastatic Merkel Cell Carcinoma

Abstract

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.

Should we be Afraid of Immune Check Point Inhibitors in Cancer Patients with Pre-Existing Rheumatic Diseases? Immunotherapy in Pre-Existing Rheumatic Diseases

“… 14 A case of sarcoidosis deterioration with hypercalcemia treated with steroids in a patient with skin cancer on anti-PDL1 has also been reported. 39 In a study by Sakakida et al, 2 patients with pre-existing untreated sarcoidosis experienced no worsening. 40 One out of two patients developed thyroid dysfunction after anti-PD1 treatment.…”

“…Together, 19% and 25% of patients reported in literature experienced a relapse of the pre-existing autoimmune disease or de novo irAEs, respectively. 14 , 17 , 20 – 22 , 26 , 30 , 39 , 40 Data on patients on ICIs with pre-existing sarcoidosis indicate that PAD flare or irAEs could happen but can be managed with steroids.…”

An atypical sarcoid-like reaction during anti-protein death 1 treatment in a patient with metastatic melanoma

“…After four cycles of pembrolizumab, restaging by 18 F-FDG PET/CT demonstrated stable disease with persisting FDG-avid metastatic mediastinal lymph nodes. Treatment with pembrolizumab was continued and in March 2018, a partial response of the mediastinal lymph nodes was documented, which was confirmed in June 2018.…”

“…In November 2017, the patient underwent 18 F-FDG PET/CT imaging as part of his follow-up, which revealed enlarged, FDG-avid mediastinal and hilar lymph nodes. Transbronchial biopsy of the lesions was performed guided by endobronchial ultrasound (EBUS) for pathological examination, which confirmed the diagnosis of relapsed melanoma (stage IV-M1a, according to the AJCC 8th edition; BRAF wild type).…”

“…Rarely, sarcoidosis preexists or is a paraneoplastic syndrome whereby a more profound exacerbation under ICI has been described [17]. A correlation has been reported between the incidence of sarcoid-like reactions and baseline presence of higher T-helper-17 cell counts in peripheral blood prior to anti-PD-1 treatment [18]. This might indicate that preexisting characteristics of the host immune system such as Th17 immunity play a role in the development of sarcoid-like reactions under ICI.…”