Electrochemotherapy as a Trigger to Overcome Primary Resistance to Anti-PD-1 Treatment: A Case Report of Melanoma of the Scalp

Abstract

BackgroundImmunotherapy with immune checkpoint inhibitors is one of the main therapies for advanced melanoma. Nevertheless, albeit remarkable, immunotherapy results are still unsatisfactory as more than half of patients progress, and resistance to treatment still has a dramatic impact on clinical outcomes. Local treatments such as radiotherapy or electrochemotherapy (ECT), in addition to local control with palliative intent, have been shown to release tumoral neoantigens that can stimulate a robust systemic antitumor immune response.Case PresentationWe report the case of a patient with multiple nodular melanoma lesions of the scalp initially treated with local ECT. Soon after the procedure, multiple new lesions appeared close to the treated ones, therefore the patient started a systemic treatment with the anti-PD-1 nivolumab. The lesions of the scalp did not respond to immunotherapy, presenting a loco-regional spreading. To control the bleeding and painful lesions, we performed a second ECT, while continuing systemic immunotherapy. The treated lesions responded to the second procedure, while the other lesions continued progressing in number and dimension. Unexpectedly, after 2 months from the second ECT, the patient presented a progressive shrinkage of both treated and untreated lesions until complete remission. Concomitantly, he developed immune-related adverse events including grade 4 thyroid toxicity, grade 2 vitiligo-like depigmentation and grade 2 pemphigoid. At present, after 18 months from the first ECT and 14 months from the starting of anti-PD-1 immunotherapy, the patient is in good clinical condition and complete remission of disease still persists.ConclusionThis case highlights the potential role of ECT in increasing tumor immunogenicity and consequently in inducing a powerful immune response overcoming primary resistance to checkpoint inhibitor immunotherapy.

Electrochemotherapy combined with immunotherapy – a promising potential in the treatment of cancer

“…Nearly complete response was eventually obtained after the treatment with ipilimumab and was present at 6-months followup (65). Two other case reports also demonstrated beneficial effects of combined treatment with electrochemotherapy and ICIs (66,67).…”

Electrochemotherapy and immune interactions; A boost to the system?

“…A 39 year old patient with stage II metastatic melanoma was treated with PD-1 CPI and ECT as a 5th line treatment, and the patient does not show any sign of disease reoccurrence 4 years after the treatment [29]. A further case report indicated that repeat ECT treatments are still effective for local tumour burden reduction when being used before PD-1 CPI and also after PD-1 CPI [30]. Quaresmini et al concluded that their case report highlights the possibility of ECT to increase tumour immunogenicity, thus leading to an increase response to CPI.…”

Potential dual synergy between electrochemotherapy and sequence of immunotherapies in metastatic melanoma: A case report

“…However no data from trials exist to evaluate the potential role of the combination or the correct sequence of these two therapeutic options-loco-regional and systemic treatment-but only anecdotic/retrospective cases in papers. Moreover, nowadays it is unknown the appropriate timing and sequence in terms of restoring efficacy of immunotherapy in resistance events (9)(10)(11)(12)(13).…”