Clonal hematopoiesis (CH) is a blood-cell precursor state tied to higher risk of blood cancers, and radiation may worsen it. Researchers analyzed blood samples from TheraP, a randomized trial comparing 177Lu-PSMA-617 radioligand therapy with cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer. Baseline CH was common (77%) and similar between arms. By progression, new treatment-emergent CH appeared in 62% of patients given 177Lu-PSMA-617 versus 40% given cabazitaxel. The DNA damage response gene PPM1D made up 42% of the radioligand-emergent mutations. CH clones also expanded more often (71% vs. 30%), and growth rose with the number of treatment cycles. The authors conclude that 177Lu-PSMA-617 strongly promotes CH and support longitudinal monitoring for long-term blood-related complications as the therapy moves earlier in care.
