Long-term Safety and Cumulative Efficacy of Multicycle 177 Lu-DOTA-IBA Therapy in Bone Metastases: A Retrospective Cohort Study.

Abstract

To evaluate the long-term efficacy, safety, and survival outcomes of at least 4 treatment cycles of 177 Lu-DOTA-IBA therapy in patients with bone metastases. This single-center retrospective cohort study enrolled patients with bone metastases who initiated therapy between November 2021 and May 2024 and completed ≥4 cycles of 177 Lu-DOTA-IBA. The primary endpoints were symptom improvement [Numerical Rating Scale (NRS) and Karnofsky Performance Status (KPS)], safety (Common Terminology Criteria for Adverse Events v5.0), and overall survival. Longitudinal efficacy changes were analyzed using linear mixed-effects models. Fifty-six patients were included: 31 completed 4-5 cycles and 25 completed 6-10 cycles. Pharmacokinetic analysis (n=20) demonstrated a longer effective half-life in lesions than in the whole body, with progressively increasing target-to-nontarget uptake ratios over time. Treatment-related myelosuppression of any grade occurred in 8 patients (14.3%), renal toxicity in 4 (7.1%), and grade 3 thrombocytopenia in 1 (1.8%); no other grade 3-4 adverse events were observed. Increasing treatment cycles were not associated with increased hematological or renal toxicity. The best overall pain response rate (NRS reduction ≥50%) was 88.5%, and KPS improvement was observed in 79.6% of patients. Longitudinal analysis demonstrated cumulative therapeutic benefit, with continuous NRS reduction and KPS improvement across cycles. Disease progression during treatment independently predicted shorter survival. For patients with bone metastases who can tolerate multicycle therapy, long-term 177 Lu-DOTA-IBA treatment yields cumulative symptom improvement with no significant increase in cumulative toxicity risk, supporting its use as a long-term therapeutic strategy.