Eye immune privilege? Nivolumab plus ipilimumab: successful treatment in a patient with cutaneous melanoma and ocular metastases

Fernandez-Diaz, Amaya B; García-Medina, Adrian; Ferrer-Guillén, Blanca; Berrocal, A.

doi:10.1097/cmr.0000000000000591

Cited by 5 publications

(5 citation statements)

References 8 publications

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“…10 In fact, in some subgroups of patients, the beneficial effects of immunotherapy on CNS metastasis are striking, with similar intracranial and extracranial response rates to nivolumab plus ipilimumab. 11,12 This begs the question of whether the eye responds similarly, 13 and therefore, whether local treatments (radiation, intravitreous melphalan, etc.) are necessary for these eyes.…”

Section: Discussionmentioning

confidence: 99%

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition

et al. 2020

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Purpose: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored.Design: Multicenter, retrospective cohort study.Participants: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. Methods: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye.Main Outcome Measures: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes.Results: The median age at presentation of ophthalmic disease was 66 years (range, 23e88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5e38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30e40 Gy) in 6 eyes, intravitreous melphalan (10e20 mg) in 4 eyes, enucleation

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Section: Discussionmentioning

confidence: 99%

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition

et al. 2020

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“…49,50 Finally, successful antitumor treatment with intravenous-administered monoclonal antibodies has also been reported in cases of metastatic ocular lymphoma and melanoma. 51,52 In this study, we first examined GD2 expression and the immune cell profile of retinoblastoma and then investigate the antiretinoblastoma effects of dinutuximab and CD16-expressing NK-92MI cells.…”

Section: Introductionmentioning

confidence: 99%

<p>Dinutuximab Synergistically Enhances the Cytotoxicity of Natural Killer Cells to Retinoblastoma Through the Perforin-Granzyme B Pathway</p>

Wang

Yang

Pan

et al. 2020

OTT

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Conventional chemotherapy and enucleation usually fail to cure advanced retinoblastoma. We investigated the retinoblastoma immune microenvironment and the efficacy of the combination of dinutuximab and CD16-expressing NK-92MI (NK-92MI hCD16-GFP ) cells on retinoblastoma cells in this study. Patients and Methods: Immunohistochemistry and flow cytometry (FC) were performed to assess the expression level of GD2 in retinoblastoma tissues and cells. Gene set enrichment analysis (GSEA), immunohistochemisrztry and immunocytochemistry were conducted to assess the retinoblastoma immune microenvironment and the integrity of the blood-retinal barrier (BRB). After overexpressing CD16 in NK-92MI cells, fluorescence-activated cell sorting (FACS) was applied to select the positive subpopulation. LDH assays and FC were used to detect LDH release and apoptosis in retinoblastoma cells subjected to a combination of dinutuximab and NK-92MI hCD16-GFP cells. Finally, the release of perforin-granzyme B and the expression of CD107a in NK-92MI hCD16-GFP stimulated by retinoblastoma cells were assessed via enzyme-linked immunosorbent assays (ELISAs) and FC in the presence of dinutuximab or an isotype control. Results: GD2 was heterogeneously expressed in retinoblastoma tissues and cell lines and positively correlated with proliferation and staging. GSEA revealed the immunosuppressive status of retinoblastoma microenvironment. The immune cell profile of retinoblastoma tissues and vitreous bodies suggested BRB destruction. LDH release and apoptosis in retinoblastoma cells caused by NK-92MI hCD16-GFP cells were significantly enhanced by dinutuximab. Finally, the release of perforin-granzyme B and the expression of CD107a in NK-92MI hCD16-GFP cells stimulated by retinoblastoma cells were obviously increased by dinutuximab. Conclusion: This study indicates that retinoblastoma impairs the integrity of the BRB and contributes to dysregulated immune cell infiltrates. GD2 is a specific target for natural killer (NK) cell-based immunotherapy and that the combination of dinutuximab and NK-92MI hCD16-GFP cells exerts potent antitumor effects through antibody-dependent cell-mediated cytotoxicity.

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“…7 Only a few studies of immune checkpoint inhibitors (ICIs) treatment for ocular metastases have been published, indicating that evidence of immunotherapy for ocular metastases is limited and deserves further exploration. 8 Iris metastases are often associated with neovascularization, and antineovascularization is often used to treat iris metastases. 2 For this patient, we used anlotinib for antineovascularization.…”

Section: Discussionmentioning

confidence: 99%

“…Immunological responses to antigens from the eye are significantly attenuated 7 . Only a few studies of immune checkpoint inhibitors (ICIs) treatment for ocular metastases have been published, indicating that evidence of immunotherapy for ocular metastases is limited and deserves further exploration 8 …”

Section: Discussionmentioning

confidence: 99%

Iris metastasis as resistance mechanism to atezolizumab, carboplatin, and etoposide but responds to additional irinotecan and anlotinib in a small cell lung cancer patient

Huang

Zhang

2023

Thoracic Cancer

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Small cell lung cancer (SCLC) is an aggressive malignancy associated with poor prognosis. Metastasis to sites outside the chest at the time of initial diagnosis, such as bone, brain, and liver metastasis have been found in most SCLC patients. Iris metastases from SCLC have rarely been previously reported, and often cause eye pain and blindness in patients. Here, we report a patient with SCLC who presented with iris metastasis in the right eye and metastasis in the left adrenal gland due to disease progression on first‐line therapy, which subsequently caused pain and blindness in the right eye. The patient was treated with second‐line irinotecan combined with anlotinib and atezolizumab and did not receive any local treatment in the right eye. After only one cycle of treatment, the iris metastases in the right eye were smaller than before, and the visual acuity in the right eye recovered. At the same time, her left adrenal metastases were also significantly smaller than before. Our case suggests that systemic therapy with effective treatment options can similarly improve iris metastases in patients.

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Eye immune privilege? Nivolumab plus ipilimumab: successful treatment in a patient with cutaneous melanoma and ocular metastases

Cited by 5 publications

References 8 publications

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition

<p>Dinutuximab Synergistically Enhances the Cytotoxicity of Natural Killer Cells to Retinoblastoma Through the Perforin-Granzyme B Pathway</p>

Iris metastasis as resistance mechanism to atezolizumab, carboplatin, and etoposide but responds to additional irinotecan and anlotinib in a small cell lung cancer patient

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