Impact of Modern Systemic Therapies and Clinical Markers on Treatment Outcome for Metastatic Melanoma in A Real-World Settins

We commend Krakowski I, et al. [1], for their recent article describing a recent prospective study that analyzes the treatment response, prognosis, and prognostic factors in metastatic melanoma patients receiving immune checkpoint inhibitors (ICIs) and MAPKinase inhibitors (MAPKis). In their study investigating current first-line systemic therapy, the authors confirmed that ICIs and MAPKis are effective treatments in advanced melanoma patients in a real-world setting, comparable to prior clinical trials. Although both therapies demonstrated significant improvements in the survival of patients with metastatic melanoma, the study highlighted the superiority of ICIs compared to MAPKis with regards to complete response, progression free survival, and overall survival [1]. The results of this study further supports current guidelines that indicate the use of ICIs as first-line treatment for advance melanoma due to the impressive efficacy and safety profile of ICIs [2]. However, this study utilizes data from 2010 to 2017, which does not reflect the impact that the recent Covid-19 pandemic has on cancer patients undergoing ICI therapy.

It is well established that patients with cancer are at a considerably higher risk of contracting Covid-19 with increased severity and mortality compared to non-cancer patients, largely believed to be due to the immunosuppressive state of many cancer patients [3]. Recent studies further investigated any additional Covid-19 related risks associated with ICI use in cancer patients. One study by Bersanelli M, et al. [4], demonstrated that symptomatic cases of Covid-19 in cancer patients being treated with ICIs were found to have a higher prevalence, hospitalization, and mortality rate [4]. Moreover, another study conducted by Coperchini F, et al. [5], details the increased risk of immunerelated adverse events, such as cytokine release syndrome (CRS) which is a fatal manifestation of Covid-19, in patients treated with ICIs [5]. It is evident that our present understanding of the health risks associated with the use of ICIs does not encompass the novel health-care related issues that were introduced during the pandemic and is likely to persist for years to come. Due to the new adverse findings associated with ICI use that were brought to light by the onset of the Covid-19 pandemic, the previously established safety and risk to benefit ratio of ICI therapy in the management of advanced melanoma should be reevaluated..

It is evident that the Covid-19 pandemic has placed significant strain on the health-care system worldwide that will likely shape the way we practice medicine for the foreseeable future. With this in mind, further investigation on the risks associated with ICI use is necessary in order to optimize the management of advanced melanoma. Although we applaud the work of Krawkowski I, et al. [1], the results of their study that support ICIs as an effective and safe first-line systemic therapy for metastatic melanoma, does not reflect the substantial and long-lasting impact of the Covid-19 pandemic on the present state of global health. The current guidelines regarding the management and treatment of advanced melanoma should be reassessed and updated to encompass the added risks associated with Covid-19.

None.

The authors declare no competing interests.

1. Krakowski I, Bottai M, Häbel H, Masucci G, Girnita A, et al. (2021) Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real-world setting. J Eur Acad Dermatol Venereol 35(1): 105-115.
2. Barrios DM, Do MH, Phillips GS, Postow MA, Akaike T, et al. (2020) Immune checkpoint inhibitors to treat cutaneous malignancies. J Am Acad Dermatol 83(5): 1239-1253.
3. Tian J, Yuan X, Xiao J, Zhong Q, Yang C, et al. (2020) Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. Lancet Oncol 21(7): 893-903.
4. Bersanelli M, Giannarelli D, De Giorgi U, Pignata S, Di Maio M, et al. (2020) Symptomatic COVID-19 in advanced-cancer patients treated with immune-checkpoint inhibitors: prospective analysis from a multicentre observational trial by FICOG. Ther Adv Med Oncol 12: 1758835920968463.
5. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M (2020) The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 53: 25-32.