Bone marrow impairment during early [Lu-177]PSMA-617-Radioligand Therapy: hematotoxicity or tumor progression?

Ziel/Aim In radioligand therapy with [Lu-177]PSMA-617 (PSMA-RLT), the comparably low absorbed bone marrow dose allows for multiple therapy cycles with relatively low risk of hematological adverse events (hAE). However, disease progression itself may be a cause of bone marrow impairment (BMI). The aim of this study was to assess the relationship between BMI and response to treatment.

Methodik/Methods Hematological parameters (HP), i.e., hemoglobin concentration, platelet count and white blood cell count, of 64 patients with mCRPC were assessed over two cycles of PSMA-RLT until restaging after 12 to 16 weeks (no previous PSMA-RLT). In retrospect, development of HP was analyzed both qualitatively according to CTCAE-criteria and quantitatively, taking into account also the extent of bone involvement (BI) (PROMISE) into account. Percentage changes of HP from baseline (Δ%HP) were compared to quantitative and qualitative biochemical (PCWG3) and imaging response based on PET volumetry.

Ergebnisse/Results Qualitatively, all grade 3/4 hAE were associated with disseminated or diffuse BIand biochemical non-response at restaging. Quantitatively, at baseline, HP inversely correlated with biochemical and volumetric tumor burden as well as BI pattern (p<0.05). Among patients with disseminated or diffuse BI, Δ%HP at restaging inversely correlated with percentage changes in PSA and tumor volume on PET (p≤0.017). Biochemical non-responders showed a significant decrease in Δ%HP (p≤0.001) while biochemical responders retained stable blood counts (p≥0.079).

Schlussfolgerungen/Conclusions Qualitative and quantitative BMI during PSMA-RLT appears to be closely associated with osseus tumor burden as only patients with advanced BI and non-response to therapy exhibited high-grade hAE as well as a significant decline of HP. This implies that in patients with advanced mCRPC non-response to PSMA-RLT may be a major cause of BMI during early treatment cycles.

Publication History

Article published online:
14 April 2022