The following article features coverage from the European Society of Medical Oncology (ESMO) Congress 2021. Click here to read more of Hematology Advisor’s conference coverage.

Among patients with relapsed or refractory classical Hodgkin lymphoma treated with nivolumab, low tumor microenvironment (TME) levels of M2 macrophages appear to positively correlate with complete response (CR) rate, according to research presented at the European Society of Medical Oncology (ESMO) Congress 2021.

The TME in patients with Hodgkin lymphoma has previously been implicated in disease progression and prognosis. Previous research has established, for example, that inhibitory immune checkpoint inhibitors may be overexpressed in the disease microenvironment, potentially hindering an immune response.

It is, however, unclear the role that M2 macrophages and other cell types in the Hodgkin lymphoma TME play in overall patient prognosis. For this retrospective study, researchers evaluated tumor samples of patients with classical Hodgkin lymphoma treated with nivolumab to determine cell positivity for a number of markers, and to link any evaluated biomarkers with patient prognosis, including progression-free survival (PFS).

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Overall, samples from 61 primary tumors and 15 repeated samples from patients with relapse or disease progression after nivolumab were included. The researchers investigated the relationship between M2 macrophage levels (using CD163/c-MAF as a proxy), and cells positive for CD68, PD-1, LAG-3, TIM-3, CTLA-4, or TIGIT, and CR rate and PFS.

Among patients with low CD163 levels, the 4-year PFS rate was 24.1% and the median PFS was 11.6 months. Patients with high CD163 levels, however, had a 4-year PFS of 42.6% and a median PFS of 24.8 months, highlighting a significant difference between the 2 groups (P =.0086).

Lower M2 levels in primary samples were, furthermore, linked with a greater likelihood of CR with nivolumab (P =.047).

A comparative analysis between baseline and post-treatment samples suggested that LAG-3-positive and PD-1-positive cell levels increased with treatment, while CD68-positive and CD163-positive cell levels decreased.

“We found that low number of CD163+ cells in primary samples were associated with inferior PFS during [nivolumab] therapy, while a lower level of M2 was correlated with achievement of CR,” the authors wrote. “In repeated biopsies after [nivolumab] therapy the cell profile in the TME changed: number of PD-1+ and Lag-3+ T-cells increased and number of CD68+ and CD163+ macrophages decreased.”

Read more of Hematology Advisor’s coverage of ESMO 2021 by visiting the conference page.


Fedorova L, Gusak A, Lepik K, et al. Immune microenvironment in classical Hodgkin lymphoma: composition and dynamics in patients with relapsed/ refractory disease. Presented at: European Society of Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 832MO.