Skin cancers

Confocal images can help monitor melanoma response to checkpoint inhibitors


Reflectance confocal microscopy may be a useful non-invasive technique for evaluating early treatment response to immune checkpoint inhibitors in patients with melanomas, according to Australian clinicians.

The technique may be particularly helpful in the setting of unresectable primary disease, according to Dr Genevieve Ho and colleagues at the Melanoma Institute Australia and University of Sydney.

They note that little data is available on the response of primary cutaneous melanomas to checkpoint inhibitors because primaries are usually excised for diagnosis or definitive surgical treatment. Traditional investigations such as surgery or histological evaluation are invasive, while imaging techniques such as CT and ultrasound are suboptimal for cutaneous disease.

However they report on the case of a 40-year old male patient with unresectable Stage IIIB primary scalp melanoma that highlighted how in vivo reflectance confocal microscopy was able to assist in monitoring treatment response to immunotherapy.

The patient received upfront systemic treatment with combination anti-PD1 (nivolumab) and anti-LAG3 (relatlimab) as part of a clinical trial after clinicians judged that surgical resection would have been challenging, highly morbid, and would have a high risk of development of in-transit metastases and locoregional disease.

Treatment response was assessed radiologically and reflectance confocal microscopy was also performed with a Vivascope 3000 on the 3-4 cm2 primary melanoma and metastases to explore and describe features of treatment response.

Initially there were numerous large heterogenous nests of bright, pleomorphic round cells and cerebriform nests seen in the upper dermis, consistent with invasive melanoma.

At six weeks after starting treatment, the primary melanoma and in-transit metastases were similar in size clinically, and confocal images showed abundant melanophages and inflammatory cells at the upper dermis, without any atypical cells or cerebriform nests of melanoma cells.

After a further ten weeks of treatment, all tumours were smaller and the patient displayed vitiligo-like depigmentation on his body. Confocal images revealed dermal melanophages amongst prominent collagen bundles. This observation was supported by histological evaluation of a punch biopsy of the primary melanoma that showed no residual viable melanoma.

Confocal images also showed numerous pigment-laden macrophages in the superficial dermis associated with fibrosis and lymphocytes consistent with regression.

Dr Ho and colleagues said the features of response to checkpoint inhibitors observed in confocal images were similar to those seen when evaluating pathological response to treatment in melanoma specimens resected after neoadjuvant immunotherapy, which include an inflammatory infiltrate and features of healing and repair.

They said the findings from this individual case suggested that monitoring response with confocal microscopy may assist clinicians in decision making on whether to start or delay upfront systemic treatment in patients with unresected primary melanomas

However they acknowledged that reflective confocal microscopy was limited by loss of depth resolution, and it would therefore be used for accessible superficial cutaneous and mucosal lesions.

“It may not be possible to confirm complete tumour response with RCM alone if the residual extends further than 0.2mm deep but it may facilitate accurate biopsy and can characterise the tumour microenvironment,” they wrote.

Nevertheless, the case “highlights the potential role of RCM as a complementary tool in monitoring treatment response in the rapidly evolving field of drug therapy for melanoma, particularly in the setting of unresectable primary disease,” they concluded.

The findings are published in the Journal of the European Academy of Dermatology and Venereology.

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