SAT-473 - A Real-World, Single Center Retrospective Cohort Study of 177 Lu-DOTATATE Therapy in Metastatic or Inoperable Pheochromocytoma/Paraganglioma

Multiple trials have reported that peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is an effective treatment option for patients with metastatic pheochromocytoma/paraganglioma (PPGL). We describe our real-world experience with PRRT via a standard four-cycle protocol with a focus on toxicity, including dosimetry. Patients with a Krenning score of 3-4 via somatostatin-receptor imaging were eligible. Thirteen patients (7F, 6M) with metastatic or inoperable PPGL were analyzed following a minimum of two cycles of 177Lu-DOTATATE between 2018 – 2025. Median age at diagnosis was 48 years; median age at treatment was 55 years. Genetic testing was performed in 12 (92%) patients, seven (58%) of whom carried a germline pathogenic variant in succinate dehydrogenase subunit B. PRRT was first line systemic therapy in eight (62%), second line in three (23%), and third line in two (15%) patients. Eleven (85%) patients completed the intended four-cycle therapy; two terminated treatment early in the setting of progression (1) and toxicity (1). Of those who completed therapy, three (30%) received re-treatment. Best tumor response via RECIST 1.1 was assessed in twelve patients. Average length of follow-up was 15 months. Three (25%) demonstrated partial response (PR), seven (58%) stable disease, and two (17%) had progressive disease. The only patient with an inoperable primary tumor experienced PR and underwent a subtotal surgical resection with a subsequent 13-fold decrease in plasma metanephrines (MN). Alpha blockade was present in eight (62%) patients. No patient required inpatient admission or other intensive monitoring and there were no incidences of hypertensive crisis or catecholamine release syndrome. The most common treatment-related adverse events (TRAE) were hematologic, with early cessation of therapy in two patients (15%) for grade 3+ myelosuppression – (1) with pre-existing transfusion dependent anemia and (1) who developed myelodysplastic syndrome complicated by neutropenic fever resulting in death following cycle 7 of re-treatment. Dosimetry was available for six (46%) patients. Following four cycles, five (83%) had cumulative renal absorbed doses (AD) below the generally considered dose limit ( < 23 Gy) while one (17%) had a cumulative renal AD of 27 Gy, with grade 2 nephrotoxicity. AD to other organs were within normal ranges. For indexed tumors, the mean AD was 15 ± 14 Gy/cycle. With an overall disease control rate of 83%, PRRT with 177Lu-DOTATATE is a viable option for patients with metastatic or inoperable PPGL. Despite 77% of patients with pre-therapy elevations in plasma MN more than 4x/URL, there were no cardiovascular complications; however, there were significant hematologic TRAEs, likely in the setting of increased skeletal burden of metastases and/or previous cytotoxic chemotherapy warranting caution and potential dose reductions in this population.