PRIMARY MEDIASTINAL B‐CELL LYMPHOMA IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS

Abstract

Although previously characterized as a subtype of diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL) is a now recognized as a distinct subtype of NHL with unique clinical and biologic features, many of which overlap with classic Hodgkin lymphoma. PMBCL has a peak incidence in the adolescent and young adult (AYA) population and, unlike other subtypes of NHL, a higher incidence among females. Recent studies into the molecular biology of PMBCL have revealed frequent amplifications in 9p24.1 which includes the locus for PD-L1 and genomic alterations in CIITA, CD58, B2M, which likely further contribute to tumor immune evasion. Treatment for PMBCL varies across centers with no single standard of care. When treated on historic pediatric protocols designed for mature B-NHL, children and AYAs with PMBCL have inferior outcomes compared to patients with DLBCL treated on the same protocol. Recent clinical trials have sought to improve outcomes in PMBCL with the addition of rituximab with and modifications to pediatric regimens and/or the adoption of the dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) chemotherapy regimen. Despite this, outcomes in prospective multicenter trials remain suboptimal. There is strong rationale for immune checkpoint blockade in PMBCL including the key molecular features outlined above as well as data from phase II trials in adults showing efficacy of pembrolizumab and nivolumab in the relapsed setting. As such, we are now conducting a phase III trial evaluating the role of nivolumab in addition to chemotherapy for children and adults with previously untreated PMCBL. In this session we will review the current state of the science in PMBCL and provide an update on our ongoing phase III trial. Keywords: extranodal non-Hodgkin lymphoma, non-Hodgkin (pediatric, adolescent, and young adult) No conflicts of interests pertinent to the abstract.