Lutetium-177 Dotatate-Induced Hemolytic Anemia and Myelodysplastic Syndrome

Abstract

Lutetium-177 ( 177 Lu) dotatate is a type of peptide receptor radioligand therapy (PRRT) using radiolabeled somatostatin for patients with progressive somatostatin receptor-positive gastrointestinal neuroendocrine tumors. While cases of therapy-related myeloid neoplasms (t-MN) have been described as a consequence of 177 Lu dotatate, there are no reports of hemolytic anemia associated with therapy. We present a case of a 68year-old woman with metastatic low-grade neuroendocrine tumor who presented four weeks after the second dose of 177 Lu dotatate with progressive fatigue and dyspnea. Laboratory workup was remarkable for hemolytic anemia. Lutetium-177 dotatate-induced hemolysis was suspected after ruling out other causes. Corticosteroid treatment was initiated with improvement in hemoglobin, and dose-reduced PRRT was planned upon discharge. Six months into the treatment course of 177 Lu dotatate, macrocytic anemia was noticed on routine follow-up with normal vitamin B12 and folic acid levels. A bone marrow biopsy was done, revealing myelodysplastic syndrome (MDS) features. Given the temporal relationship between drug introduction and the objective findings, early-onset 177 Lu dotatate-induced MDS was diagnosed with a plan for close hematologic follow-up. Myelodysplastic syndrome should be suspected when megaloblastic anemia develops in patients with previous 177 Lu dotatate therapy. The latency period between initial treatment and MDS diagnosis reported in the literature ranges between 15 months to seven years. Apart from the unusually early onset of MDS, what is unique about our case is the development of hemolytic anemia after administration of PRRT. The clinical course and the brisk response to steroid therapy, suggest other mechanisms of PRRT toxicity besides DNA breaks, genetic mutations, and myelosuppression by an immunemediated component that likely plays a role in 177 Lu dotatate toxicity. Further investigation and monitoring are needed to identify the frequency of such adverse events and the pathophysiology of their occurrence.

Long-Term Complications of Radioligand Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms

“…The difference in observed adverse events percentage may arise from fact, that Sarit et al, were analyzing acute and chronic complications combined in all timeline of the observation. Nevertheless, there are some cases of serious adverse events (SAEs) during RLT in the literature, but can be considered as very rare [ 9 ].…”

Targeted radionuclide therapy in endocrine-related cancers: advances in the last decade

“…However, this result was not statistically significant, likely due to lack of power to detect OS differences and the effects of crossover after progression on high-dose octreotide. Toxicity with Lu-177 DOTATATE arm has generally been mild, with most side effects limited to minor nausea, fatigue, and reversible myelosuppression (38,(40)(41)(42)(43)(44). The risk of treatment-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is estimated to be 2-3% and typically develops more than 2 years after completion of therapy (34,39,40).…”

“…The risk of treatment-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is estimated to be 2-3% and typically develops more than 2 years after completion of therapy (34,39,40). Sequential or combination therapy with alkylating-based chemotherapy agents may result in a higher risk of developing a long-term hematologic toxicity, with some series reporting up to a 10-20% risk (43)(44)(45)(46)(47)(48)(49)(50). Renal toxicity has been negligible, likely due to the nephroprotective amino-acid infusion administered alongside the PRRT (42,(51)(52)(53).…”