Post hoc analysis compares clonal hematopoiesis after 177Lu-PSMA-617 versus cabazitaxel, suggesting monitoring is essential.
Key Points
This research investigates the prevalence of clonal hematopoiesis after 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer and its comparison to cabazitaxel chemotherapy.
Post hoc analysis using serial blood samples from a randomized phase II trial in prostate cancer.
Deep error-corrected targeted sequencing of cell-free DNA and leukocyte DNA.
Defined treatment-emergent clonal hematopoiesis by detecting mutations at progression not present at baseline.
Analyzed samples from 178 patients with paired baseline-progressive samples.
77% of patients had baseline clonal hematopoiesis, similar across both treatment groups.
Treatment-emergent clonal hematopoiesis occurred more frequently in the 177Lu-PSMA-617 group (62% vs 40% for cabazitaxel; P=0.03).
42% of emergent mutations were linked to the gene PPM1D in the 177Lu-PSMA-617 group, with increased odds ratios for treatment-emergent clonal hematopoiesis and PPM1D.
Clonal expansion occurred more frequently with 177Lu-PSMA-617, and CH variant frequency increased with the number of cycles given.