Nodular lymphocyte-predominant Hodgkin lymphoma: advances in disease biology, risk stratification, and treatment

Abstract

Recent updates have detailed how patients with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) may be better risk stratified using prognostic scoring systems. Most patients with NLPHL present with early-stage disease and have an indolent disease course. To reflect these differences from classic Hodgkin lymphoma, nomenclature has been updated to recognise nodular lymphocyte predominant B-cell lymphoma as an alternative to NLPHL. The Global NLPHL One Working Group have published their pivotal dataset in 2024 which challenges the prognostic significance of variant immunoarchitectural (IAP) patterns and proposes a new prognostic scoring system. Key identified prognostic factors include age >45 years, stage III-IV disease, haemoglobin <105 g/L and splenic involvement. After multivariate analysis, variant IAP was not shown to be associated with inferior outcome. As most patients with NLPHL have excellent long-term survival, identifying patients where treatment de-escalation is appropriate will help to minimise toxicity. De-escalation strategies include observation after fully resected stage I disease, active surveillance, anti-CD20 antibody monotherapy, radiotherapy in early-stage disease and avoiding anthracycline or bleomycin containing chemotherapy regimens. Evidence supporting the use of novel therapies remains limited with disappointing results from a recently published study of ibrutinib in patients with relapsed NLPHL. Hopefully, future trials will investigate novel agents such as checkpoint inhibitors, T cell engaging antibodies and chimeric antigen receptor-T cell therapy.