Hematologic changes under [¹⁷⁷Lu]Lu-DOTA-TATE PRRT in GEP-NETs: a long-term longitudinal cohort study

Abstract Background Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE is increasingly applied for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This study aimed to characterize the development of hematologic parameters under PRRT in a large single-center cohort. We retrospectively analyzed 178 patients with GEP-NETs treated with [¹⁷⁷Lu]Lu-DOTA-TATE at a university hospital (2012–2023). Hemoglobin (Hb), white blood cell count (WBC), and platelet count (PLT) were assessed at baseline, after 2 cycles (FU1), after 4 cycles (FU2), during post-therapy follow-up (FU3), and at the last available timepoint (FU4). Patients with deteriorating blood values during or after therapy were categorized according to CTCAE v6.0. The occurrence of myelodysplastic syndrome (MDS) within the period from completion of the initial PRRT to initiation of salvage chemotherapy or PRRT was investigated. Results Baseline mean values were Hb, 13.6 ± 1.6 g/dL; WBC, 6.9 ± 2.0 × 10⁹/L; and PLT, 256 ± 92 × 10⁹/L. A significant decline in those hematological parameters was observed at FU1 and FU2 ( p < 0.01). Between FU2 and FU3, values recovered significantly ( p < 0.001), with no further relevant change at FU4 for Hb and PLT, while WBC increased significantly compared to FU3. At last follow-up (FU4), all parameters remained significantly below baseline (all p < 0.001), but exhibited final values in a normal laboratory range (Hb, 12.4 ± 1.9 g/dL; WBC, 6.3 ± 2.6 × 10⁹/L; and PLT, 216 ± 78 × 10⁹/L). Based on CTCAE v6.0, only 4 patients (2%) developed grade 3 hematological adverse events and no grade 4 adverse event was observed. After completing four cycles of PRRT, 2 patients (1.3%) developed MDS according to the WHO criteria. Patients with chemotherapy prior to PRRT ( n = 30) had lower baseline WBC and showed smaller on-treatment declines, but were the only subgroup without Hb recovery from the nadir (median change FU2 to FU4, − 0.35 vs. +0.35 g/dL; adjusted p = 0.017). Conclusion PRRT with [¹⁷⁷Lu]Lu-DOTA-TATE induces a mild short to midterm decline in hematologic parameters, which is followed by a significant increase during long-term follow-up, eventually returning to values within the laboratory reference range. Serious adverse events or MDS are very rare, supporting long-term overall hematologic safety.