Correct!
4. 1 and 3

A slight increase in sarcoidosis has been reported in melanoma (0.58%) compared to 0.005% in the general population (4). Both nivolumab and ipilimumab have been reported to induce a sarcoid-like granulomatosis reaction (5-7). Based on these reports his chemotherapy was stopped and he was treated with oral corticosteroids, prednisone initially 60 mg/day followed by tapering doses over 3 months. Three months later a repeat PET/CT of his chest did not show any areas of increased tracer uptake (Figure 4).

Figure 4. Representative images from PET/CT of chest 3 months after nivolumab and ipilimumab were stopped and corticosteroids were begun.

No other areas of increased tracer uptake were observed. Clinically he is doing well off chemotherapy and off corticosteroids.

Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. As these and other immune checkpoint inhibitors are increasingly used in malignancies such as non-small cell cancer of the lung, it seems likely that the sarcoid-like reaction observed in this patient may become more common. 

References

  1. Eltawansy SA, Panasiti R, Hasanien S, Lourdusamy D, Sharon D. Metastatic malignant melanoma of the inguinal lymph node with unknown primary lesion. Case Rep Med. 2015;2015:879460. [CrossRef] [PubMed]
  2. Um SW, Kim HK, Jung SH, et al. Endobronchial ultrasound versus mediastinoscopy for mediastinal nodal staging of non-small-cell lung cancer. J Thorac Oncol. 2015 Feb;10(2):331-7. [CrossRef] [PubMed]
  3. Gogas H, Eggermont AM, Hauschild A, et al. Biomarkers in melanoma. Ann Oncol. 2009 Aug;20 Suppl 6:vi8-13. [CrossRef] [PubMed]
  4. Seve P, Schott AM, Pavic M, Broussolle C, Gilis L, Thomas L. Sarcoidosis and melanoma: a referral center study of 1,199 cases. Dermatology. 2009;219(1):25-31. [CrossRef] [PubMed]
  5. Gogas H, Eggermont AM, Hauschild A, Hersey P, Mohr P, Schadendorf D, Spatz A, Dummer R. Biomarkers in melanoma. Ann Oncol. 2009 Aug;20 Suppl 6:vi8-13. Danlos FX, Pagès C, Baroudjian B, et al. Nivolumab-induced sarcoid-like granulomatous reaction in a patient with advanced melanoma. Chest. 2016 May;149(5):e133-6. [CrossRef] [PubMed]
  6. Suozzi KC, Stahl M, Ko CJ, et al. Immune-related sarcoidosis observed in combination ipilimumab and nivolumab therapy. JAAD Case Rep. 2016 Jul 14;2(3):264-8. [CrossRef] [PubMed]
  7. Reuss JE, Kunk PR, Stowman AM, Gru AA, Slingluff CL Jr, Gaughan EM. Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report & review of the literature. J Immunother Cancer. 2016 Dec 20;4:94. [CrossRef] [PubMed]

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