Main Session
Sep
28
PQA 03 - Digital Health Innovation and Informatics, Patient Safety & Quality, and Radiation and Cancer Biology
2556 - Metabolic Profiling as a Predictor of Hematopoietic Adverse Events in Patients Receiving ¹77Lu-PSMA-617 Radioligand Therapy
Presenter(s)
Neil Mookerjee, MD - Thomas Jefferson University, Philadelphia, PA
N. Mookerjee1, S. Xu2, J. R. Rocchetti3, N. Francois2, P. T. Tran4, L. J. Wilson5, J. W. DiNome1, and N. L. Simone2; 1Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, 2Dept. of Radiation Oncology, Sidney Kimmel Medical College and Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA, 3Thomas Jefferson University Hospital, Pennsylvania, PA, 4Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5St. Jude Children's Research Hospital, Memphis, TN
Purpose/Objective(s):
¹77Lu-PSMA-617 improves cancer outcomes and quality of life for metastatic castration-resistant prostate cancer. Significant interpatient variability exists in treatment-related toxicity, and to date, toxicity has primarily been associated with tumor burden and bone marrow involvement. We hypothesized that metabolic characteristics, specifically body mass index (BMI) and diabetes status, modify hematologic and renal toxicity during therapy.Materials/Methods:
We performed a single-institution retrospective review of 89 patients treated between 2022 and 2025 with 200 mCi of ¹77Lu-PSMA-617 for up to 6 cycles. Clinical variables, including BMI and diabetes status, were collected. Laboratory markers of hemoglobin (HGB), white blood cell count (WBC), platelet count (PLT), and glomerular filtration rate (GFR) were recorded at baseline and after each cycle. Percent change from baseline was calculated for each laboratory parameter. Longitudinal trajectories of percent change were modeled using linear mixed-effects models with patient-level random intercepts and fixed effects for timepoint, BMI group (<25 vs =25 kg/m²), and a time-by-BMI interaction term. Cumulative percent decline at cycle 4, selected as a clinically meaningful and commonly completed treatment time point, was compared between BMI groups using two-sample t-tests (a = 0.05).Results:
The mean age was 71 years, 78.7% were overweight or obese (BMI =25 kg/m²), and 28.1% had diabetes. Treatment was associated with significant overall declines in PLT (20.0%) and HGB (5.5%) from baseline (both p = 0.01), while changes in WBC and GFR over time were not statistically significant. Patients with BMI <25 kg/m² experienced significantly greater platelet decline compared with overweight/obese patients at cycle 4 (48.7% vs 25.9%; p = 0.02), and this association remained significant in mixed-effects modeling. No significant differences in WBC, HGB, or GFR trajectories were observed by BMI or diabetes status. Diabetes was not independently associated with differential hematologic or renal changes over time.Conclusion:
This is a novel exploration of metabolic factors in ¹77Lu-PSMA-617 therapy, demonstrating that obesity and diabetes were not significantly associated with differential toxicity, while normal-weight patients were more susceptible to greater platelet declines. These findings suggest BMI could inform risk-stratified hematologic monitoring and personalized management in ¹77Lu-PSMA-617 therapy. Larger, multicenter prospective studies evaluating metabolic states as modifiers of toxicity are warranted to validate this association and refine patient selection and toxicity mitigation strategies.