Introduction of immune checkpoint inhibitors (ICI) revolutionized the treatment of relapsed/refractory classical Hodgkin lymphoma (r/r cHL). However, continuous ICI treatment in responding patients (pts) poses a risk of immune-related toxicity and introduces a significant financial burden, raising the question of optimal therapy duration. There is an unmet need for the novel biomarkers to optimize the ICI treatment strategy. We characterized the concentrations of serum soluble programmed death-ligand 1 (sPD-L1), interleukin-6 (IL-6) and interleukin-15 (IL-15) during nivolumab (nivo) therapy and their association with clinical factors, treatment safety and survival.
We analyzed serum samples from 52 pts with r/r cHL, who received nivo at Pavlov University. At the nivo start 36 pts (70%) had B-symptoms and 38 pts (73%) had extranodal lesions; there was no active infections. Dose of nivo was 3 mg/kg iv q2w until unacceptable toxicity or treatment change due to disease progression. Median follow-up was 53 mo (20-61). Four-year overall survival (OS) was 93%, 4-year PFS was 26 % (median 20.6 mo). Serum levels of IL-6, IL-15, sPD-L1 were determined by ELISA before nivo therapy and at 3-6 mo after the treatment start.
Before treatment the mean level of IL-6 was 7,98 pg/ml (SD=26.3), IL-15 – 12,33 pg/ml (SD=33.6), PD-L1 – 9,9 pg/ml (SD=3.5). At the nivo start higher IL-6 was associated with B-symptoms (p=0.0086) and extranodal involvement (p = 0.0026). Both biomarkers significantly decreased after treatment (p < 0.01). sPD-L1 correlated with tumor volume before nivo initiation (correlation coefficient = 0.4, p=0.0093). Lower IL-6 before therapy was associated with advantage in PFS from the start of ICI (median PFS – 23.7 mo vs 12.6 mo, p=0.029; cut-off - 2.2 pg/ml) and decrease in the time to response (median – 2.8 mo vs 8.1 mo).
sPD-L1 level has positive correlation with tumor volume before the nivolumab treatment start. IL-6 and sPD-L1 resulted in a significant decrease after nivolumab treatment. Serum IL-6 was predictive regarding PFS and time to response from the start of nivolumab. Addional studies are required to assess the predictive value of IL-6.
Clinical trial identification
This study was supported by BMS research grant CA209-8EG
Legal entity responsible for the study
This study was supported by BMS research grant CA209-8EG.
All authors have declared no conflicts of interest.