Abstract 1412P
Background
As previously reported, enza increases natural killer cells (NK) and decreases myeloid-derived suppressor cells (MDSCs) in biochemically recurrent (BCR) prostate cancer without ADT (Madan et al JITC, 2021). Enza’s immune impact in mCRPC with ADT has not been reported. This information could be important for developing new immunotherapy strategies in prostate cancer where PD1/PDL1 inhibition are not effective in unselected patients (pts).
Methods
Pts with mCRPC who had progression on ADT alone were randomized to either enza or enza+prostvac(P), a therapeutic cancer vaccine targeting PSA. Pts were followed for time to progression (TTP). Peripheral blood was assessed at baseline and at 1 month for 10 parental cell types (CD4+ and CD8+ T cells, T-regulatory cells, NK, NK-T cells, conventional and plasmacytoid dendritic cells, B cells, monocytes, and MDSCs) and 148 refined subsets related to their maturation/function. Serum IL-8 cytokine levels were also evaluated.
Results
57 pts were enrolled. The median age of all pts was 57 years (47-94) and median PSA was 15.02 (0.55-587). Median TTP was 23.3 months for all pts, with no differences between the arms. 24 pts were evaluated for immune responses: 12 with enza alone, and 12 with enza+P. Pts treated with enza had trends of increases in NK cells (n=12, p=0.064) and increases in MDSC (p=0.042) at 1 month vs baseline. With enza alone, increases in subsets of monocytes and MDSCs were associated with shorter TTP. With enza+P, increases in NK after 1 month were also seen (p=0.064), and greater increases in PD-L1+ mature NK were associated with longer TTP. No changes or associations with TTP were seen among T-cells, B-cells or dendritic cells. Among all pts, IL-8 decreases at one month were associated with longer TTP.
Conclusions
Enza in first-line treatment of mCRPC with ADT was associated with increased NK and MDSC; drops in IL-8 levels were associated with better TTP. This compares to enza in BCR without ADT where NK were also increased, but MDSC were decreased, and IL-8 was unchanged. NK which have been associated with better outcomes in prostate cancer are increased after enza in mCRPC and these findings could inform future immunotherapy strategies.
Clinical trial identification
NCT01867333.
Editorial acknowledgement
Legal entity responsible for the study
Clinical Center, National Cancer Institute.
Funding
EMD Serono.
Disclosure
All authors have declared no conflicts of interest.