Immune Checkpoint Inhibitors In Pediatric Malignancies, Efficacy And Adverse Events In Alexandria University

Abstract

Background: Pediatric malignancies are the most fatal childhood diseases in developed countries, with survival rates reaching over 80% in high-income countries and 15-45% in low- and middle-income countries. Immune checkpoint inhibitors (ICI), including monoclonal antibodies against negative regulators of T-cell function, such as CTLA-4, Programmed Death-1 (PD-1), and PD-L1, have improved outcomes in adult cancer. Results of ICI in pediatric malignancies were all disappointing which highlight the need to improve outcomes by further studies. Methods: This retrospective study included 31 eligible patients from 1-20 years old to discusses the experience of Alexandria clinical oncology department and Borg el Arab pediatric oncology center, in using immune checkpoint inhibitors (ICI) in pediatric patients, with the primary goal of assessing efficacy and the secondary is evaluating the safety profile. Results: Thirty one eligible patients aged 1-20 from May 2018 to May 2023, with a male-to-female ratio of 1.38:1, and the average age at diagnosis was 14.39 years old. The majority of cases (19 patients) were diagnosed with classical Hodgkin lymphoma, followed by Xeroderma pigmentosa. Pembrolizumab was the most commonly used drug. The mean PFS was 25.5 months, while the mean OS was 27 months. Side effects of ICI was found and documented in 11 patients (35.5%). Thyroiditis was found in nearly half of the patients, followed by colitis and dermatitis, all of which were grade II. Hodgkin lymphoma and Xeroderma pigmentosa showed the highest response to ICI compared to other diagnoses. Conclusions: immune checkpoint inhibitors are effective in pediatric malignancies, especially in Hodgkin disease and Xeroderma pigmentosa, with a very good safety profile and response rate. Further studies should be applied to verify predictive markers to know the best responders among patients.