Predictive role of the Hodgkin lymphoma-associated cytokines: a prospective study of the Czech Hodgkin Study Group
Prognostic stratification and thus the selection of the frontline treatment in Hodgkin lymphoma (HL) is based on historical systems which only indirectly reflect lymphoma burden or cytokine activity. Analysis of the lymphoma-related soluble biomarkers offers a non-invasive tool for more precise risk stratification.
To define a prognostic significance of the pretreatment soluble cytokines levels in the newly diagnosed pts with HL treated within GHSG policy
We have conducted prospective serum sampling (2017-2021) of the unselected pts treated in three university hospitals in the Czech Republic. All samples were analysed centrally using ELISA for lymphoma cells (TARC pg/ml; sCD30, ng/ml), macrophages (sCD163, ng/ml) and inflammation-related cytokines (sIL-6, pg/ml). Clinical and laboratory data were retrieved from the national Hodgkin lymphoma registry.
In total we have analysed 169 (100%) consecutive pts. Median age was 42 (19-83) yrs, with slight female predominance (52%). All but 7 pts (96%) have been diagnosed as classical HL (nodular sclerosis in 83, mixed cellularity in 58, lymphocyte-rich in 8 and lymphocyte depletion in 1, 12 not classified). Ann Arbor stages were as follows: (12%), II (37%), III (22%), IV (29%) with B-symptoms present in (56%) and extranodal disease in (32.5%) of the pts, leading to allocating of the pts into limited (18%), intermediate (24%) and advanced (58%) GHSG stages. Treatment was based on ABVD (48%), BEACOPPesc (42%), COPP/ABV (8%), or other (2%) regimen. Treatment response was assessed in 161 pts (95%), with CR in 90 % of the pts. After a median FU of 43 months the 5-y OS reached 90.4% (95% CI 0.83-0.98) and 5-y PFS 86.6% (95% CI 0.81-0.93). Lower mean pretreatment levels of 3 cytokines correlated with achieving of CR: sCD30 (70 vs 130; p=0.04), sCD163 (783 vs 1171; 0.007), sIL-6 (26 vs 130; p<0.001), TARC did not show any correlation with CR (mean 33764 vs 23702; p=0.67). Two cytokines were predictive for PFS: sCD30, cut-off 90 ng/ml (5-y PFS 79.1 vs 90.4%; p=0.044) and sIL-6, cut-off 9 pg/ml (5-y PFS 80.3 vs 92.5%; p=0.023). High levels of sCD30 and sIL-6 were associated with inferior 5-y OS of 79.3 vs 97.2% (sCD30, p=0.004) and 82.6% vs 97.4 % (sIL-6, p=0.025).
Pretreatment levels of soluble CD30 and IL-6 are associated with the treatment outcome and survival in the patients treated with GHSG risk-adapted policy.
MZCR-RVO (FNOL, 00098892), AZV NU22-03-0018