Effect of bone marrow disease on hematologic toxicity and response to [¹⁷⁷Lu]Lu-PSMA-617 therapy: insights from...

Despite the effectiveness of [¹⁷⁷Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC), hematologic toxicity remains a concern, particularly in patients with bone metastases. This study evaluated whether the extent, intensity, and heterogeneity of bone disease on pretreatment PSMA-PET/CT were associated with hematologic toxicity, PSA response, and overall survival (OS) in mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-617.

This retrospective study included 96 mCRPC patients who underwent pretreatment PSMA-PET/CT and received standard-of-care [¹⁷⁷Lu]Lu-PSMA-617. Hematologic toxicity, PSA responses, and OS were analyzed in relation to quantitative PET parameters, including tumor volume, SUVmean, and heterogeneity of PSMA uptake in bone metastases.

Clinically significant hematologic toxicity occurred in 19 patients (19.8%). Treatment discontinuation was more likely in those with a significantly higher (p = 0.007) percentage of total bone volume with PSMA-avid disease (median 28% vs. 1.7%). Those requiring dose delays or reductions (median 21% vs. 1.5%), blood transfusions (median 21% vs. 1.4%), and platelet transfusions (median 32% vs. 1.8%) also exhibited higher median percentages of total bone volume involvement (all p < 0.01). Patients with more heterogeneous PSMA uptake had lower PSA50 response rates than those with more homogeneous uptake (30.3% vs. 64.5%, p = 0.002). A > 50% difference between PSMA-low and PSMA-high bone disease was associated with significantly shorter OS (p < 0.001).

Extensive PSMA-avid bone involvement was associated with increased hematologic toxicity in mCRPC treated with [¹⁷⁷Lu]Lu-PSMA-617. Greater heterogeneity in PSMA uptake correlated with lower PSA50 response and OS but not hematologic toxicity. Careful patient selection and monitoring are needed, particularly in those with widespread bone disease.