9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial

Elena Gerhard-Hartmann*, Helen Goergen, Paul J Bröckelmann, Anja Mottok, Tabea Steinmüller, Johanna Grund, Alberto Zamò, Susana Ben-Neriah, Stephanie Sasse, Sven Borchmann, Michael Fuchs, Peter Borchmann, Sarah Reinke, Andreas Engert, Johanna Veldman, Arjan Diepstra, Wolfram Klapper, Andreas Rosenwald

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

High programmed cell death 1 ligand 1 (PD-L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin- and Reed-Sternberg cells (HRSC) have been shown to be associated with favourable response to anti-PD-1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD-L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti-PD-1-based first-line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced-stage or r/r cHL. All but two cases (97%) showed PD-L1 expression by the tumour cells in variable amounts. While MHC-I was rarely expressed in >50% of HRSC, MHC-II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD-L1 and MHC-I/II expression on early response to the highly effective anti-PD-1-based NIVAHL first-line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti-PD-1 first-line cHL treatment.

Original languageEnglish
Number of pages11
JournalBritish Journal of Haematology
DOIs
Publication statusE-pub ahead of print - 14-Sep-2021

Keywords

  • fluorescence in situ hybridisation
  • CD274
  • classical Hodgkin lymphoma
  • immune checkpoint blockade
  • major histocompatibility complex
  • SINGLE-ARM
  • PD-L1 IMMUNOHISTOCHEMISTRY
  • BRENTUXIMAB VEDOTIN
  • DIAGNOSTIC-TOOL
  • NIVOLUMAB
  • BLOCKADE
  • TRANSPLANTATION
  • MULTICOHORT
  • MULTICENTER
  • FAILURE

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