PDF herunterladen
Klin Monbl Augenheilkd 2016; 233(04): 540-544
DOI: 10.1055/s-0042-102668
Kasuistik
Georg Thieme Verlag KG Stuttgart · New York

Intraocular Inflammation Associated with New Therapies for Cutaneous Melanoma – Case Series and Review

Intraokulare Entzündungen assoziiert mit neuen systemischen Therapien des kutanen Melanoms
F. C. Fierz
1   Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland (Chair: Prof. Dr. Klara Landau)
2   Department of Ophthalmology, Cantonal Hospital of Lucerne, Switzerland (Chair: Prof. Dr. Dr. M. A. Thiel)
,
F. Meier
1   Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland (Chair: Prof. Dr. Klara Landau)
,
K. Chaloupka
1   Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland (Chair: Prof. Dr. Klara Landau)
,
C. Böni
1   Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland (Chair: Prof. Dr. Klara Landau)
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
26. April 2016 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Background. In advanced cutaneous melanoma, new systemic therapies include immunotherapy by checkpoint inhibition and targeted inhibition of the mitogen-activated protein kinase pathway; these are becoming increasingly well established. We describe the clinical presentation of uveitis in three patients with concomitant systemic melanoma treatment.

History and Signs. Three patients with metastatic melanoma receiving systemic therapy (ipilimumab, vemurafenib) presented at our institution with a short history of ocular symptoms. Clinical findings included anterior uveitis, intermediate uveitis, disc swelling, inflammatory choroidal lesions and retinal vasculitis.

Therapy and Outcome. All three patients responded well to local and/or systemic steroid treatment. In one case, the systemic anti-cancer drug was discontinued after the onset of uveitis.

Conclusions. Ocular inflammation may occur in the setting of systemic melanoma therapy. Presentations of uveitis include Vogt-Koyanagi-Harada-like syndromes. Ocular inflammation can usually be controlled by topical and sometimes systemic corticosteroid therapy. However, treatment guidelines are not established and management of these patients demands close cooperation with the oncologist.

Zusammenfassung

Hintergrund. Neue systemische Therapien finden zunehmenden Einsatz in der Behandlung fortgeschrittener Melanomerkrankungen. Dazu gehören Therapien, welche die Immunantwort modulieren oder spezifisch in intrazelluläre Signalwege eingreifen. Wir beschreiben die klinische Präsentation uveitischer Erkrankungen bei 3 Patienten, welche gleichzeitig eine systemische Melanombehandlung erhalten haben.

Anamnese und Befund. Drei Patienten mit einer systemischen Melanomtherapie (Ipilimumab, Vemurafenib) haben sich in unserer Klinik aufgrund okulärer Beschwerden vorgestellt. Es zeigten sich in unterschiedlicher Kombination anteriore und intermediäre Uveitis, Papillenschwellung, entzündliche choroidale Läsionen und retinale Vaskulitis.

Therapie und Verlauf. Alle 3 Patienten haben auf lokale und/oder systemische Steroide ein gutes Ansprechen gezeigt. In 1 Fall wurde die zugrundeliegende systemische Therapie wegen der okulären Komplikationen abgesetzt.

Schlussfolgerungen. Im Rahmen systemischer Melanomtherapien können intraokulare Entzündungen auftreten, die sich unter anderem mit einem Vogt-Koyanagi-Harada-Syndrom ähnlichen Bild manifestieren. Therapeutisch werden meist lokale und manchmal auch systemische Steroide eingesetzt. Allgemeine Behandlungsrichtlinien sind aber noch nicht etabliert und im Einzelfall ist eine enge Zusammenarbeit mit dem behandelnden Onkologen erforderlich.

Key words

ocular side effects - uveitis - intraocular inflammation - Vogt-Koyanagi-Harada - ipilimumab - vemurafenib - CTLA-4-inhibition - BRAF-inhibition - immune-related adverse events

Schlüsselwörter

okuläre Nebenwirkungen - Uveitis - intraokulare Entzündung - Vogt-Koyanagi-Harada - Ipilimumab - Vemurafenib - CTLA-4-Inhibition - BRAF-Inhibition
 

  • References

  • 1 Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-2516
    CrossrefPubMedSuche in Google Scholar
  • 2 Hodi FS, OʼDay SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723
    CrossrefPubMedSuche in Google Scholar
  • 3 Tarhini A. Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. Scientifica (Cairo) 2013; 2013: 857519
    PubMedSuche in Google Scholar
  • 4 Papavasileiou E, Prasad S, Freitag SK et al. Ipilimumab-induced ocular and orbital inflammation–A case series and review of the literature. Ocul Immunol Inflamm 2015; Aug 24 [Epub ahead of print]: 1–7
    PubMedSuche in Google Scholar
  • 5 Dudley ME, Wunderlich JR, Yang JC et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005; 23: 2346-2357
    CrossrefPubMedSuche in Google Scholar
  • 6 Yeh S, Karne NK, Kerkar SP et al. Ocular and systemic autoimmunity after successful tumor-infiltrating lymphocyte immunotherapy for recurrent, metastatic melanoma. Ophthalmology 2009; 116: 981-989 e1
    CrossrefPubMedSuche in Google Scholar
  • 7 Sober AJ, Haynes HA. Uveitis, poliosis, hypomelanosis, and alopecia in a patient with malignant melanoma. Arch Dermatol 1978; 114: 439-441
    CrossrefPubMedSuche in Google Scholar
  • 8 Aisenbrey S, Luke C, Ayertey HD et al. Vogt-Koyanagi-Harada syndrome associated with cutaneous malignant melanoma: an 11-year follow-up. Graefes Arch Clin Exp Ophthalmol 2003; 241: 996-999
    CrossrefPubMedSuche in Google Scholar
  • 9 Ueda H, Howson JM, Esposito L et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423: 506-511
    Suche in Google Scholar
  • 10 Du L, Yang P, Hou S et al. Association of the CTLA-4 gene with Vogt-Koyanagi-Harada syndrome. Clin Immunol 2008; 127: 43-48
    CrossrefPubMedSuche in Google Scholar
  • 11 Sugita S, Takase H, Taguchi C et al. Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens. Invest Ophthalmol Vis Sci 2006; 47: 2547-2554
    CrossrefPubMedSuche in Google Scholar
  • 12 Attia P, Phan GQ, Maker AV et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 2005; 23: 6043-6053
    CrossrefPubMedSuche in Google Scholar
  • 13 Downey SG, Klapper JA, Smith FO et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res 2007; 13: 6681-6688
    CrossrefPubMedSuche in Google Scholar
  • 14 Weber JS, OʼDay S, Urba W et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol 2008; 26: 5950-5956
    CrossrefPubMedSuche in Google Scholar
  • 15 Robinson MR, Chan CC, Yang JC et al. Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis. J Immunother 2004; 27: 478-479
    CrossrefPubMedSuche in Google Scholar
  • 16 Yeh OL, Francis CE. Ipilimumab-associated bilateral optic neuropathy. J Neuroophthalmol 2015; 35: 144-147
    PubMedSuche in Google Scholar
  • 17 Borodic G, Hinkle DM, Cia Y. Drug-induced graves disease from CTLA-4 receptor suppression. Ophthal Plast Reconstr Surg 2011; 27: e87-e88
    CrossrefPubMedSuche in Google Scholar
  • 18 Crosson JN, Laird PW, Debiec M et al. Vogt-Koyanagi-Harada-like syndrome after CTLA-4 inhibition with ipilimumab for metastatic melanoma. J Immunother 2015; 38: 80-84
    CrossrefPubMedSuche in Google Scholar
  • 19 Wong RK, Lee JK, Huang JJ. Bilateral drug (ipilimumab)-induced vitritis, choroiditis, and serous retinal detachments suggestive of vogt-koyanagi-harada syndrome. Retin Cases Brief Rep 2012; 6: 423-426
    CrossrefPubMedSuche in Google Scholar
  • 20 Weber JS, Dummer R, de Pril V et al. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer 2013; 119: 1675-1682
    CrossrefPubMedSuche in Google Scholar
  • 21 Choe CH, McArthur GA, Caro I et al. Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib. Am J Ophthalmol 2014; 158: 831-837 e2
    CrossrefPubMedSuche in Google Scholar
  • 22 Lemech C, Arkenau HT. Novel treatments for metastatic cutaneous melanoma and the management of emergent toxicities. Clin Med Insights Oncol 2012; 6: 53-66
    PubMedSuche in Google Scholar
  • 23 Guedj M, Queant A, Funck-Brentano E et al. Uveitis in patients with late-stage cutaneous melanoma treated with vemurafenib. JAMA Ophthalmol 2014; 132: 1421-1425
    CrossrefPubMedSuche in Google Scholar
  • 24 Wolf SE, Meenken C, Moll AC et al. Severe pan-uveitis in a patient treated with vemurafenib for metastatic melanoma. BMC Cancer 2013; 13: 561
    CrossrefPubMedSuche in Google Scholar
  • 25 Joshi L, Karydis A, Gemenetzi M et al. Uveitis as a result of MAP kinase pathway inhibition. Case Rep Ophthalmol 2013; 4: 279-282
    CrossrefPubMedSuche in Google Scholar
  • 26 Draganova D, Kerger J, Caspers L et al. Severe bilateral panuveitis during melanoma treatment by dabrafenib and trametinib. J Ophthalmic Inflamm Infect 2015; 5: 17
    CrossrefPubMedSuche in Google Scholar
  • 27 Horvat TZ, Adel NG, Dang TO et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol 2015; 33: 3193-3198
    CrossrefPubMedSuche in Google Scholar
  • 28 Miserocchi E, Cimminiello C, Mazzola M et al. New-onset uveitis during CTLA-4 blockade therapy with ipilimumab in metastatic melanoma patient. Can J Ophthalmol 2015; 50: e2-e4
    CrossrefPubMedSuche in Google Scholar
  • 29 Nallapaneni NN, Mourya R, Bhatt VR et al. Ipilimumab-induced hypophysitis and uveitis in a patient with metastatic melanoma and a history of ipilimumab-induced skin rash. J Natl Compr Canc Netw 2014; 12: 1077-1081
    PubMedSuche in Google Scholar
  • 30 Liao B, Shroff S, Kamiya-Matsuoka C et al. Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro Oncol 2014; 16: 589-593
    CrossrefPubMedSuche in Google Scholar