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

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 neoplasms (tMNs), including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) 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.

We accessed the treatment files of patients with neuroendocrine neoplasms treated at our institution between January 2017 and January 2025 for pathology reports of myelodysplasia, leukemia, aplastic anemia and similar hematological disorders.

A total of 173 patients received ¹⁷⁷Lu-DOTATATE. A vast majority (77.5%) of them were treated with four therapy cycles. A total of 10/173 (5.8%) patients (4 males, 6 females) 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), six developed myelodysplastic syndrome (MDS), one developed aplastic anemia, and one developed multilineage dyspoiesis (the latter two also deemed to have MDS). Eight out of ten (80%) died after a median duration of 8 months (4.23) from tMN diagnosis. Two patients were diagnosed with AML after 2 and 4 years from the start of first cycle, while 40% of MDS cases were diagnosed by 1 year after cycle 1 of ¹⁷⁷Lu-DOTATATE. Additionally, multilineage dyspoiesis was observed at around 5 years.

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.