Nivolumab-Induced Sarcoid-Like Granulomatous Reaction in a Patient With Advanced Melanoma

Abstract

To our knowledge, we report the first case of sarcoid-like granulomatous reaction induced by nivolumab, a fully human IgG4 anti-programmed death 1 (PD-1) immune checkpoint inhibitor antibody. A 57-year-old man was treated with nivolumab 3 mg/kg for 2 weeks for a desmoplastic melanoma stage III American Joint Commission on Cancer, with no BRAF, NRAS, and cKit mutations. At 10 months, although melanoma complete response was achieved, he developed sarcoid-like granulomatous reaction in the mediastinal lymph node and skin, which resumed after nivolumab arrest. Melanoma did not relapse after 12 months of follow-up. Considering the recently demonstrated role of activated PD-1/PDL-1 axis in sarcoidosis, granulomatous reaction in the patient seems to be a paradoxical reaction, but similar observations have been reported with ipilimumab, another immune checkpoint inhibitor. Sarcoid-like granulomatous reaction during immunotherapy treatment could be a manifestation of cell-mediated immunity induced by these drugs. Impact of granulomatous reaction induced by immune checkpoint inhibitor on melanoma progression is not known and requires further study. Melanoma patients treated by immunotherapy (anti-cytotoxic T-lymphocyte-associated protein-4/anti-PD-1) should be considered for developing sarcoid-like granulomatous reaction that must not be confused with tumor progression.

Sarcoid-Like Granulomatosis Induced by Nivolumab Treatment in a Lung Cancer Patient

“…We used nivolumab as a second-line treatment for recurrent lung cancer and observed the development of granulomatous lesions. Sarcoidosis and sarcoid-like reactions have been reported when nivolumab is used alone or in combination with ipilimumab in the treatment of melanoma [1, 2, 3, 4]. It has also been reported that sarcoidosis can develop following pembrolizumab treatment in sarcoma [5].…”

“…This was a strong indication that the granuloma was a side effect of nivolumab treatment. As improvement was observed by discontinuation of nivolumab alone, we did not administer steroid treatment [3]. Additionally, follow-up observation indicated that the primary lesion did not progress after the discontinuation of nivolumab.…”

Sarcoidosis, Malignancy and Immune Checkpoint Blockade

“…For example, cases of sarcoid-like reactions have been reported following treatment of melanoma with interferon, vemurafenib, vaccine therapy, ipilimumab and nivolumab [9][10][11][12][13][14]. In our institutional experience, we have seen patients with concurrent melanoma and sarcoidosis both identified at the diagnosis of malignancy, and the development of sarcoid-like reactions, both symptomatic and asymptomatic from ICPI therapy [15].…”

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

“…Pseudoprogression, also called tumor flare, is a distinct immune-related pattern of response caused by the infiltration of immune cells to the tumor site that can manifest in the form of an apparent increase in tumor size, the development of new lesions, or a mixed response such as progression and regression of different tumors in the same patient [112,113]. The development of granulomatous changes in the lymph nodes resembling progression have also been described during immunotherapy treatment [114]. In studies investigating immunotherapies in patients with cancer, the prevalence of pseudoprogression can vary based on tumor type; for example, it has been reported to be 7% to 10% in melanoma [23,113,115], 5% to 7% in NSCLC [25,27], 7% in UC [54], and 0% to 2% in HNSCC [44,116].…”