Immune checkpoint inhibitors in pediatric patients with melanoma: a systematic literature review

<b>Aim:</b> This study summarized the existing evidence on the outcomes and safety of anti-PD-1s, anti-PD-L1s and anti-CTLA-4s in pediatric patients with melanoma. <b>Materials &amp; methods:</b> MEDLINE^® and Embase were searched from database inception to 01-12-2023. <b>Results:</b> Of 1537 records identified, 27 studies (k) of 64 patients were included. Most studies were case reports (k = 16). All studies used anti-PD-1s (nivolumab, pembrolizumab) alone or anti-CTLA-4s (ipilimumab). Survival outcomes (k = 7), response outcomes (k = 15) and adverse events (k = 16) varied. Safety profiles of anti-PD-1s and anti-CTLA-4s were broadly similar to that seen in adults. <b>Conclusion:</b> Despite scarce, heterogenous data, this review can be a reference for clinicians. Future clinical trials should include adolescents to grow the evidence base on immune checkpoint inhibitors in pediatric melanoma. Immune checkpoint inhibitors have been well studied and documented in adult melanoma patients; however, little evidence is available for pediatric patients. In this systematic review of studies on pediatric patients (0–21 years) with melanoma who received either monotherapy or combination treatments of anti-PD-(L)1s or anti-CTLA-4s, data were scarce and heterogenous. Of 27 unique studies including a total of 64 patients, most studies were case reports. Multi-patient studies contained few pediatric patients with melanoma. Anti-PD-1s (nivolumab or pembrolizumab) alone or anti-CTLA-4s (ipilimumab) were reported in all studies, while some studies reported use of combination therapy. No study was identified on the use of anti-PD-L1s. Survival, response and adverse events were reported variably across studies, and conclusions on apparent trends on the comparative efficacy of treatments could not be realized. Anti-PD-1s and anti-CTLA-4s showed similar safety profiles in pediatric patients compared with adults; however, this limited finding is based on few studies of small sample sizes. Clinical trial data on adolescent patients with melanoma are required to further grow the evidence base on immune checkpoint inhibitors in pediatric melanoma.