Vera Ghali, Medical Doctor Pediatrics, Allergy and Immunology, Member of the Lebanese Order of Physicians and Lebanese Pediatric Society, shared on X:
“A growing role of Immune Checkpoint Therapy (ICT) in pediatric and adolescent lymphoma. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1) inhibitors are the most commonly utilized ICTs which enhance anti-tumor immunity. ICT has demonstrated efficacy in both high-risk and relapsed disease with ongoing investigations into low-risk disease.
Given the success of ICT in pediatric Hodgkin Lymphoma (pHL), there is promise for the use of ICT in multiple subtypes of pediatric Non-Hodgkin Lymphoma with increased expression of programmed death ligand 1 (PD-L1), especially after the FDA approval of cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) inhibitor ipilimumab in 2011, and PD-L1 inhibitors nivolumab and pembrolizomab in 2014.
CTLA-4 inhibitors increase T-cell expansion by interrupting the inhibitory interaction of CTLA-4 on T-cells, whereas PD-1 inhibitors prevent T-cell exhaustion by interrupting the inhibitory interaction of PD-L1 and PD-L2 on tumor cells with PD-1 receptors on T-cells. Through both mechanisms, anti-tumor immunity is enhanced. Other immune regulatory pathways are also being explored.
Other variables that support the implementation of ICT have come to light such as the increased quantity of tumor neoantigens that have been identified as positive predictors of response to ICT, high tumor mutation burden of >10 mutations per Mb, and high microsatellite instability of >2 of 5 microsatellite repeats determined by PCR, are additional tumor agnostic companion biomarkers that support the use of ICT leading to broad-ranging applications of ICT across a multitude of subtypes of lymphoma.
Furthermore, combination therapy with ICT and various forms of cytotoxic chemotherapy, small molecule inhibitors, radiotherapy, antibody-drug conjugates, and cancer vaccines are being investigated. However, it should be emphasized that further research is needed to determine the safety and efficacy of ICT and CTLA-4 inhibitors as treatments in different histological subtypes of pediatric and adolescent lymphomas.
While ICT have shown efficacy, it can cause immune-related adverse events (irAEs) in children and adolescents like liver toxicity, pediatric endocrine AEs such as thyroid dysfunction, adrenal insufficiency, hypophysitis, acute Type 1 diabetes, severe high-grade 3 pneumonitis, neuritis, and pancreatitis. The use of ICT must be carefully weighed against toxicities in pediatric and adolescent patients who are a particularly vulnerable and fragile population.”
Title: Immune checkpoint therapy in pediatric and adolescent lymphomas
Authors: David J. Hoogstra, Ana C. Xavier, Paul Harker-Murray, Sarah Alexander, Lisa Giulino-Roth, Teresa A. Hernandez, Mitchell S. Cairo
Read the full article here.
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