Efficacy and safety of ¹⁷⁷Lu-PSMA radionuclide treatment in patients with diffuse bone marrow involvement: a multicenter retrospective study

Introduction: ¹⁷⁷Lu-labelled prostate-specific membrane antigen (LuPSMA) radionuclide therapy of metastatic castration-resistant prostate cancer is under investigation in a Phase III clinical trial (VISION:NCT03511664). However, patients with diffuse bone involvement, diagnosed with a superscan by bone scintigraphy at baseline, were excluded due to lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted PET. Materials and Methods: Efficacy was evaluated using PSA response rate, PSA progression-free survival, time-to-pain progression and overall survival. Imaging response was assessed by computer tomography (CT) using the Response Evaluation Criteria in Solid Tumors criteria (RECIST 1.1). Adverse events were graded according to CTCAE (Common Terminology Criteria for Adverse Events) v4.02.

Results: Of 352 screened patients across six centers worldwide, we identified 43 eligible patients who received overall 154 cycles of LuPSMA under clinical trials or compassionate access programmes. Median baseline PSA was 1000 (IQR 431-2151) ng/ml. PSA decrease of at least 50% was achieved in 26 (65%) patients, while median PSA progression-free survival was 4.8 (95%CI 2.4-7.1) months. Fifteen of 42 (36%) evaluable patients exhibited pain progression with a median time to pain progression of 8.3 (95%CI 5.4-11.3) months. Median overall survival was 11.6 (95%CI 8.8-14.3) months. Of 18 patients with evaluable target lesions on CT at baseline, objective response in nodal or visceral disease was reported in seven (39%) patients. Grade 3/4 anemia, thrombocytopenia and neutropenia occurred in nine (21%), ten (23%) and three (8%) patients, respectively. Of note, all patients had grade 1 anemia at baseline, with a median hemoglobin of 9.6 g/dl. Two (5%) patients experienced an adverse event that required a reduction to the LuPSMA activity beginning with the third cycle.

Conclusions: We found that, even in heavily pre-treated patients with mCRPC presenting with diffuse bone marrow involvement, LuPSMA has important clinical antitumor activity and acceptable toxicity. Acceptable safety outcomes do not support exclusion of these patients from future LuPSMA trials. They should also not be excluded from availability of LuPSMA in the real-world setting, however the toxicity and efficacy needs to be further evaluated in a prospective setting.