Therapy-related myeloid neoplasms following peptide receptor radionuclide therapy for neuroendocrine neoplasms: case series reporting characteristics and outcomes from single-centre experience.

Objective: Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTATATE is increasingly used in the treatment of metastatic neuroendocrine neoplasms (NENs). Marrow toxicity resulting in therapy-related myeloid neoplasms (t-MNs) remains a rare but fatal complication of PRRT, with a limited understanding of prognostic or predictive factors. Methods: We conducted a single-centre retrospective review of all patients with metastatic NEN who received at least one cycle of PRRT and subsequently developed t-MN confirmed on bone marrow biopsy. Results: Thirteen out of 306 patients (4.2%) developed t-MN during follow-up, confirmed on bone marrow biopsy. The median time from cycle 1 of PRRT to diagnosis of t-MN was 48.3 months (range: 5.4-110.1 months). The median number of PRRT cycles was 4 (range: 3-8). Nine (69%) patients received concomitant radiosensitising chemotherapy with capecitabine, and one (7.7%) had the combination of capecitabine and temozolomide. The median overall survival from cycle 1 of PRRT was 61.9 months (range: 18.5-112.2 months). The median overall survival from diagnosis of t-MN was 10.4 months (range: 1.9-89.3 months). An unfavourable karyotype, a higher degree of cytopaenia and a higher blast percentage in bone marrow were associated with worse survival outcomes of t-MN. Conclusions: t-MN following PRRT is an uncommon but serious complication that can occur several years after treatment. This case series highlights the poor prognosis following t-MN diagnosis, particularly if untreated. PRRT is an effective treatment modality for NEN, but prospective studies are needed to explore factors predictive of t-MN development.