Severe Cytopenias Following Radioligand Therapy: A Real-World Analysis.

Abstract

IntroductionTwo 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.PatientsAdults 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.MethodsPropensity 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.ResultsAfter 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 ConclusionThis 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.