Radiopharmaceutical Therapy with [¹⁷⁷Lu]Lu-DOTATATE in Refractory Meningiomas: Results from the French Multicenter MELUTE Cohort.

Abstract

Evidence supporting the efficacy and safety of [¹⁷⁷Lu]Lu-DOTATATE in refractory meningiomas derives mainly from small, single-center studies. The French national multicenter MELUTE study aimed to consolidate these data using a standardized regimen within a compassionate-use program approved by a national multidisciplinary tumor board. Methods: In this retrospective multicenter cohort study, patients with refractory meningiomas treated with [¹⁷⁷Lu]Lu-DOTATATE in 18 French centers between July 2022 and December 2024 were included. Treatment consisted of 7.4 GBq every 8 wk for up to 4 cycles. Clinical data (demographics, histologic World Health Organization grade [WHO], prior treatments, number of cycles, toxicity, progression, survival status as of October 1, 2025) were collected. Baseline [⁶⁸Ga]Ga-DOTATOC PET and brain MRI scans obtained before and after treatment were centrally reviewed. The primary endpoint was 6-mo progression-free survival (PFS) assessed using volumetric Response Assessment in Neuro-Oncology Group criteria. Secondary endpoints were PFS, overall survival (OS), and safety. Results: Sixty-nine patients were included (mean age, 65.1 ± 13.2 y; 52% female): 13 WHO grade 1, 42 WHO grade 2, 8 WHO grade 3, and 6 without histology. Most had prior surgery (86%) or radiotherapy (93%); 32% received prior systemic therapy. Twelve patients (17%) did not complete 4 cycles; only one discontinuation was toxicity-related. Six-month PFS was 70% (95% CI, 58.7-80.4%). Median PFS was 14.6 mo (95% CI, 13.3-18.5 mo), and median OS was 27.6 mo (95% CI, 24.2 mo to not reached). Grade 3 adverse events, mainly lymphopenia, occurred in 16%. Meningioma WHO grade independently predicted PFS, whereas higher Karnofsky performance status and corticosteroid use were protective; worse OS was associated with higher baseline tumor growth rate and prior systemic therapy. Conclusion: MELUTE demonstrates promising efficacy and favorable safety of [¹⁷⁷Lu]Lu-DOTATATE in refractory meningiomas with limited therapeutic options.