A recent case report supports the theory that inhibiting a molecular pathway called programmed cell death-1 (PD-1) may involve processes that lead to sarcoidosis in some cancer patients.
The study, “Nivolumab-related cutaneous sarcoidosis in a patient with lung adenocarcinoma,” was published in the journal JAAD Case Reports.
Sarcoidosis, as well as colitis, endocrinopathies, and dermatitis are immune-related adverse events observed in cancer patients, mainly in people with melanoma but also with lung cancer. These events have a lower incidence when cancer patients are treated with Yervoy (ipilimumab) and Opdivo (nivolumab) as monotherapy or in combination.
The study reports the case of a 63-year-old African-American woman diagnosed with stage 4 epidermal growth factor receptor mutation-negative lung adenocarcinoma, a form of non-small cell lung cancer.
The patient started treatment with four cycles of carboplatin, paclitaxel, and Avastin (bevacizumab) every three weeks, followed by Avastin maintenance therapy every three weeks.
After 14 months, the patient showed an increase in pleural metastatic disease and was administered Opdivo.
During her treatment with Opdivo, the patient developed cutaneous sarcoidosis. She then started treatment with low doses of systemic corticosteroids and prednisone, but her cutaneous sarcoidosis was resolved only after hydroxychloroquine treatment.
Hydroxychloroquine is a type of disease-modifying anti-rheumatic drug (DMARD) that regulates the activity of the immune system, which may be exacerbated in some diseases.
Opdivo is an antibody that binds PD-1, enabling the control and stimulation of the immune system to fight cancer. The U.S. Food and Drug Administration (FDA) approved its use for the treatment of metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin’s lymphoma.
The team observed that Opdivo blocked the inhibitory action of PD-1 on the immune system, enabling it to fight cancer cells.
In this particular case, however, the inhibition of PD-1 with Opdivo ultimately also led to the development of immune-related cutaneous sarcoidosis in a patient with lung adenocarcinoma.
How PD-1 leads to sarcoidosis is still unclear and requires additional studies.
“Clinicians must continue to be aware of potential [immune-related adverse events] as immune checkpoint inhibitors [like Opdivo and Yervoy] remain a part of our oncology armament,” the researchers wrote. “Although the clear mechanisms on how PD-1 is related to sarcoidosis remain elusive, its general participation in the disease process becomes more evident as new cases of PD-1 inhibitor-related sarcoidosis are reported.”