Immune biomarkers of response and resistance to ipilimumab and nivolumab in metastatic castration-resistant prostate cancer.
Apostolia M Tsimberidou, Christopher R Cabanski, Alexandra Drakaki et al.
✦ AI-curated · Sources linked
In 30 seconds
The multicenter phase II AMADEUS prostate expansion cohort evaluated escalating ipilimumab doses with nivolumab in 32 patients with metastatic castration-resistant prostate cancer, assessing disease control, tumoral CD8 changes, safety, and biomarkers. Six-month disease control rates were 33% (4 of 12) with I1+N360, 20% (1 of 5) with I3+N1, and 20% (3 of 15) with I5+N1. Tumoral CD8 percentage increased by a median of 5.0% across cohorts. The investigators reported similar disease control and immune activation with the lower-ipilimumab regimen and a more favorable safety profile.
Key findings
- Six-month disease control rates were 33% (4 of 12), 20% (1 of 5), and 20% (3 of 15) for I1+N360, I3+N1, and I5+N1, respectively.
- Tumoral CD8 percentage increased by a median of 5.0% across treatment cohorts.
- Early progression was associated with increased expression of a TREM2-associated myeloid gene signature, also enriched in two independent prostate cancer datasets.
- Higher ipilimumab doses were tolerable, while I1+N360 had a more favorable safety profile with similar disease control and immune activation.
Why it matters
The findings illustrate that immune activation and clinical disease control may not align uniformly in mCRPC, and that myeloid-associated biomarkers could help characterize early resistance. The comparison also suggests that escalating ipilimumab did not improve reported disease control in this cohort, informing the design of further studies of checkpoint combinations and biomarker-guided approaches.
What to keep in mind
The cohort included only 32 patients, with small numbers in each dose group; the abstract does not report comparative statistical testing for the regimen outcomes.