Hematological neoplasms after PRRT: experience from long term follow-up of 173 patients in a tertiary center

Abstract Objective Peptide receptor radionuclide therapy (PRRT) with Lutetium- 177 Dotatate (177Lu-Dotatate) is widely adopted as a later line treatment (second-line or subsequent therapy) for patients with somatostatin receptor positive neuroendocrine neoplasm. The registration NETTER-1 trial reported a late onset adverse event of therapy related myeloid neoplasia (tMN) myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) occurring in approximately 1% of patients. In this retrospective study, we sought to investigate the frequency of tMN in patients treated with 177Lu-Dotatate at our institution over the last 8 years and determine the treatment characteristics of patients developing tMN. Methods We accessed the treatment files of patients with neuroendocrine neoplasms treated at our institution between 01/2017 and 01/2025 for pathology reports of myelodysplasia, leukemia, aplastic anemia and similar hematological disorders. Results A total of 173 patients received 177Lu-Dotatate. A vast majority (77.5%) of them were treated with 4 therapy cycles. A total of 10/173 (5.8%) patients (4 male, 6 female) were diagnosed with tMN at a median of 23 months (5,63) after first cycle. One patient developed severe thrombocytopenia, stopped all treatments and was lost to follow-up. Two patients developed acute myelogenous leukemia (AML), 6 myelodysplastic syndrome (MDS), one developed aplastic anemia and one multilineage dyspoesis (both patients also deemed to have MDS). Eight out of ten (80%) died after median duration of 8 months (4,23) from tMN diagnosis. Two patients were diagnosed with AML after 2 and 4 years from start of first cycle. while 40% of MDS cases were diagnosed by 1 year post cycle 1 of 177Lu-Dotatate. Additionally, multilineage dyspoesis was observed at around 5 years. Conclusions The prevalence of tMN was 5.8% in our patient population. We have noted a higher than previously reported percentage of myelodysplasia post PRRT, especially with additional treatments and longer follow-ups.