Radioligand Therapy with 177Lu-PSMA-617 in Patients with Diffuse Bone Marrow Involvement: Safety and Efficacy Results

1280 Introduction: Advanced stage metastatic prostate cancer with extensive bone marrow involvement is related to a high risk of chemotherapy-induced myelotoxicity and poor prognosis. The role of radioligand therapy (RLT) with 177Lu-PSMA-617 in this subset of patients remains to be elucidated. This study aims to assess safety and efficacy of RLT in a patient cohort presenting with diffuse bone marrow involvement. Methods: Twenty-nine patients with progressive metastatic prostate cancer and diffuse marrow involvement (dmi based on the PROMISE miTNM classification) were treated with RLT. A mean activity of 6.6± 1.1 GBq 177Lu-PSMA-617 was administered in a median of 4 treatment cycles (IQR 2 to 6) at standard intervals of 6-8 weeks. Mean cumulative activity was 29.7± 3.7 GBq. Hematological and renal parameters were measured at baseline, prior to each treatment course, 2-4 weeks thereafter and throughout follow-up. Toxicity was classified using Common Terminology Criteria for Adverse Events v5.0. Response assessment was based on 68Ga-PSMA-PET/CT imaging (PERCIST) and serial PSA sampling (PCWG3). Results: Significant hematotoxicity (grade 3 to 4) was induced in 9 (31%) patients necessitating transfusion therapy in 8 (28%) cases of severe anemia and 3 (10%) cases of severe thrombopenia. All cases of significant hematotoxicity were reversible during a median follow-up of 6 months (IQR 2 to 12). One patient developed grade 4 nephrotoxicity which could be attributed to postrenal obstruction. Treatment response consisted of partial response in 15 (52%), stable disease in 7 (24%), and progressive disease in 7 (24%) patients. Median progression free survival (PFS) was 9 months (95% CI [6.3, 11.7]). Objective response translated into significantly prolonged PFS (2.0 vs. 12.0 months, p<0.001).Conclusion: RLT with 177Lu-PSMA-617 in patients with diffuse bone marrow involvement can be performed with an acceptable risk profile and may contribute to prolonged disease control. Diffuse bone marrow involvement should therefore not routinely be considered an exclusion criterion for RLT.