PD-L1 AND MHC-II AS PROGNOSTIC FACTOR IN HODGKIN LYMPHOMA

As reported in the Journal of Clinical Oncology, Roemer et al found that programmed death cell ligand 1 (PD-L1) expression and major histocompatibility complex (MHC) class II positivity on Hodgkin Reed-Sternberg (HRS) cells may predict favorable outcome with programmed cell death protein 1 (PD-1) inhibitor treatment in classical Hodgkin lymphoma.

HRS cells are able to evade antitumor immunity through several mechanisms, including gains of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) and perturbed antigen presentation.

Study Details

In the study, HRS cells from archived tumor biopsies from patients with relapsed/refractory disease receiving nivolumab (Opdivo) in the CheckMate 205 trial were assessed for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD-L1 and the antigen presentation pathway components β2-microglobulin, MHC class I, and MHC class II by immunohistochemistry.

Associations With Outcome

There was a significant association between PD-L1 expression and magnitude of 9p24.1 copy number alterations in HRS cells (P = .001). Patients with tumors exhibiting higher-level 9p24.1 copy gain (P < .001) and increased PD-L1 expression (P = .026) had improved progression-free survival. HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or progression-free survival (P = .07/ P = .38) with nivolumab therapy. HRS cell expression of MHC class II was predictive of complete remission (P = .03). MHC class II expression on HRS cells was not predictive of progression-free survival in patients who received nivolumab ≤ 12 months after myeloablative autologous stem-cell transplantation (ASCT), but was associated with prolonged progression-free survival among those treated > 12 months after ASCT (P = .014).

The investigators concluded, “Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In [classical Hodgkin lymphoma], clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.”

The study was funded by National Institutes of Health grants, Miller Family Fund, and Bristol-Myers Squibb.

Margaret A. Shipp, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.