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Updated: Oct 19, 2026
Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Severe Cytopenias Following Radioligand Therapy: A Real-World Analysis
Robert Yuan1, Benyamin Yaniv1, Petros Grivas2
1Department of Medicine, UMass Chan Medical School, Worcester, MA.
Introduction:
Two radiopharmaceuticals are approved for metastatic castration-resistant prostate cancer (mCRPC): Radium-223 and 177Lu-PSMA-617. While short-term hematologic toxicity is well-studied, the long-term risk of severe cytopenias and therapy-related myeloid neoplasm (t-MN) remains unclear. We compared the risk of severe cytopenias between these 2 agents.
Patients:
Adults with prostate cancer with ≥ 1 administration of 177Lu-PSMA-617 or Radium-223. Exclusion criteria included pre-existing grade ≥ 3 cytopenias in the 30 days prior to first infusion and receipt of alternate radiopharmaceutical.
Methods:
Propensity score matching (PSM) was based on age, race, and prior cancer-directed therapies. Primary endpoints were risk of grade ≥ 3 anemia, thrombocytopenia, and neutropenia, assessed at early (0-12 weeks), intermediate (12-36 weeks), and late (> 36 weeks) timepoints from first infusion.
Results:
After PSM, 1015 patients remained in each group with well-balanced baseline characteristics. Radium-223 was associated with higher risk of grade ≥ 3 anemia across all 3 time windows compared with 177Lu-PSMA-617: early (12.3% vs. 7.4%, RR 1.67, P < .001), intermediate (25.5% vs. 13.5%, RR 1.89, P < .001), and late (27% vs. 13.9%, RR 1.94, P < .001). Radium-223 was associated with higher risk of grade ≥ 3 thrombocytopenia in the intermediate (10.7% vs. 6.7%, RR 1.60, P = .001) and late time windows (11.1% vs. 7.1%, RR 1.57, P = .001) as well as higher risk of grade ≥ 3 neutropenia in the intermediate (3.9% vs. 1.9%, RR 2.10, P = .006) and late time windows (4.5% vs. 2.6%, RR 1.77, P = .01).
Conclusion:
This large, real-world study demonstrated that Radium-223 is associated with significantly higher risk of severe cytopenias compared with 177Lu-PSMA-617. Findings may inform appropriate patient selection, and sequencing of radiopharmaceutical therapy. Future studies aimed at evaluating the bone marrow environment may further elucidate the potential for clonal hematopoiesis and therapy-related myeloid neoplasms.