Checkpoint Inhibitors Immunotherapy in Metastatic Melanoma: When to Stop Treatment?

Background: Immune checkpoint inhibition (ICI) has significantly improved the survival of metastatic melanoma (MM) with a significant proportion of patients obtaining long-lasting responses. However, ICI also exposes patients to new, heavy, and sometimes irreversible toxicities. Thus, identifying the minimal amount of treatment time is extremely urgent. Methods: We researched English peer-reviewed literature from electronic databases (MEDLINE and PubMed) until July 2022 with the aim of evaluating the clinical outcomes after the cessation of ICI therapy due to elective study plans, clinician-patient sharing, and adverse events. Results: Although most of the data are from retrospective studies, considering that most patients with major responses maintain it after treatment cessation, it is proposed that for complete response (CR)/near CR, a further six months of therapy after best response may be considered enough. For partial response (PR) or stable disease (SD), treatment must be continued for at least 2 years and, in some cases, indefinitely, based on residual disease, the patient's will, and the toxic profile. Of note, in spite of the best response, 25-30% of patients relapsed, and, when retreated, responded far less than in front-line treatment. Conclusions: Most of the data being from retrospective and heterogeneous experiences, their grade of evidence is limited and no consensus has been reached on the optimal treatment duration. Controlled prospective studies are needed.