The New York Eye Cancer Center, Suites 5A/B, 115 East 61st Street, New York, NY, 10065, USA.
New York University Cancer Institute, 160 East 34th Street, New York, NY, 10016, USA.
J Immunother Cancer. 2019 Mar 25;7(1):83. doi: 10.1186/s40425-019-0555-7.
Herein, we describe the use of systemic immunotherapy for both locally advanced and metastatic conjunctival melanoma. Current treatments for advanced conjunctival melanoma typically result in poor local control leading to disfiguring orbital exenteration surgery. Locoregional spread of conjunctival malignant melanoma typically requires pre-auricular and cervical lymph node dissection with post-operative adjuvant radiation therapy. In addition, classic systemic chemotherapy has been unsuccessful in the treatment of metastatic disease.
This is a retrospectively analyzed clinical case series of 5 patients with biopsy proven conjunctival melanoma who were treated with checkpoint inhibition therapy. Of these, 3 patients were treated for residual ocular disease present after failing multiple local therapies and refusing orbital exenteration surgery and two (with local ocular control) for metastatic conjunctival melanoma. Both those with locally advanced disease and patients with metastatic disease received an anti-PD1 agent in combination with another immunotherapeutic agent. All 5 were given multiple cycles of systemic anti-PD1 therapy, 1 was initially treated with single agent ipilimumab (3 mg/kg) prior to approval of anti-PD1 agents and two received interferon eye drops. As part of each ophthalmic examination, photographs of all conjunctival and eyelid surfaces were obtained. Systemic evaluations involved initial staging scans as well as periodic re-imaging.
All cases have shown responses. Of the 2 complete responses, 1 was a patient with systemic disease. No patients developed ocular toxicity or loss of vision. However, systemic adverse effects included adrenal insufficiency, Grade-III colitis, Grade-II dermatitis, Grade-II hepatotoxicity and Grade-II pneumonitis.
This report suggests that systemic immunotherapy with or without topical interferon is effective in treatment of malignant melanoma of the conjunctiva. Therefore, it can be considered for patients with advanced local conjunctival melanoma, those who refuse orbital exenteration surgery and those with systemic metastasis.
在此,我们描述了全身性免疫疗法在局部晚期和转移性结膜黑色素瘤中的应用。目前,治疗晚期结膜黑色素瘤的方法通常导致局部控制不佳,导致毁容性眼眶切除术。结膜恶性黑色素瘤的局部区域扩散通常需要进行耳前和颈部淋巴结清扫术,并在术后进行辅助放射治疗。此外,经典的全身化疗在治疗转移性疾病方面均不成功。
这是一项回顾性分析的 5 例结膜黑色素瘤活检证实患者的临床病例系列研究,这些患者接受了检查点抑制治疗。其中 3 例患者因多次局部治疗失败后仍存在眼部疾病且拒绝接受眼眶切除术而接受治疗,另外 2 例(局部眼部控制)患者因转移性结膜黑色素瘤而接受治疗。局部晚期疾病和转移性疾病患者均接受了抗 PD-1 药物联合另一种免疫治疗药物治疗。所有 5 例患者均接受了多个周期的全身性抗 PD-1 治疗,1 例患者在批准抗 PD-1 药物之前曾接受过单药伊匹单抗(3mg/kg)治疗,2 例患者接受了干扰素滴眼剂治疗。作为每次眼科检查的一部分,均获得了所有结膜和眼睑表面的照片。全身评估包括初始分期扫描以及定期再成像。
所有病例均显示出反应。2 例完全缓解中,有 1 例为全身性疾病患者。没有患者出现眼部毒性或视力丧失。然而,全身性不良反应包括肾上腺功能不全、III 级结肠炎、II 级皮炎、II 级肝毒性和 II 级肺炎。
本报告表明,全身性免疫疗法联合或不联合局部干扰素治疗结膜黑色素瘤是有效的。因此,对于局部晚期结膜黑色素瘤患者、拒绝眼眶切除术的患者以及有全身转移的患者,可以考虑采用这种方法。