Endocrine Abstracts

Background: Due to both efficacy and tolerability, peptide receptor radionuclide therapy (PRRT) utilizing Lutetium-177 (¹⁷⁷Lu) DOTATATE has led to a paradigm shift in the treatment of advanced gastroenteropancreatic neuroendocrine tumors. As we gain more clinical experience with PRRT, we continue to understand more about treatment timing, sequencing of therapy, and optimal patient selection. One of the more well-known toxicities of PRRT is bone marrow toxicity, namely cytopenias and the dreaded treatment related myeloid neoplasms. Of particular interest is whether bone marrow toxicity is accentuated in patients with extensive bone metastasis. We sought to build on this body of literature and evaluate the hematological safety as well as the efficacy of 177Lu PRRT in the setting of advanced NETs with extensive/Confluent bone metastases.

Methods: We retrospectively reviewed the medical records of all Mayo Clinic patients (pts) with extensive/innumerable osseous metastases, defined as >50 % skeletal involvement by positron emission tomography (PET) DOTATATE, who were treated with ¹⁷⁷Lu DOTATATE. Further we divided patients into “confluent/near confluent” or “extensive” bone metastases depending on the extent of bone involvement. Patients’ characteristics, along with laboratory results before, during, and after treatment were collected. Hematotoxicity was graded according to the NCI-CTCAE v5.

Results: In total, 158 cycles of PRRT were performed in 48 pts with extensive bony metastases. The median number of PRRT cycles was 4 (range 1-8), with a cumulative dose of 29.6 GBq (+/- 1000 mCi) per patient. Four patients had dose reduction of 3.7 GBq (+/- 100 mci) per cycle due to preexisting renal dysfunction, while one pt had dose reduction due to hematological toxicity. Out of 48 patients, 24 (50%) pts experienced bone marrow toxicity of any grade after treatment with one or more cycles of PRRT. Significant grade 3-4 hematological toxicity was observed in 14 pts (29%) (Thrombocytopenia 19%, followed by anemia 14.5% and neutropenia 10%). Ten pts (21%) continued to experience cytopenia(s) of any grade six months post-PRRT. Regarding t-MNs, one patient developed therapy related myelodysplastic syndrome (2%), while two pts were found to have therapy related clonal cytopenias (t-CC) (4%).

Conclusions: In one of the largest institutional series of PRRT in patients with advanced NETs and extensive/confluent bone metastases, moderate rates of grade 3-4 hematotoxicity were observed, although the majority were transient. Our study highlights the importance of carefully monitoring and assessing hematological parameters in patients being considered for ¹⁷⁷Lu DOTATATE with extensive/innumerable bone metastasis.

ABSTRACT ID28539