Safety and Feasibility of [ 177 Lu] Lu-PSMA Therapy in Glioblastoma

Glioblastoma (GBM) is the most common primary malignant tumor of the brain with high morbidity and mortality without an effective therapeutic option currently. This study aimed to evaluate the feasibility and safety of [ 177 Lu] Lu-prostate-specific membrane antigen (PSMA) therapy in patients with progressive/persistent refractory glioblastoma.

This is a prospective single-arm pilot clinical trial with inclusion of 10 patients with progressive/persistent GBM on standard of care therapy. After evaluation of eligibility by [ 99m Tc] Tc-PSMA single-photon emission computed tomography (SPECT)/ low-dose CT, the patients received 2-6 cycles of 100-150 mCi with 4-5 weeks interval, and toxicity was assessed with regular hematologic and renal function tests as well as clinical history and examination. The response to therapy was also evaluated with magnetic resonance imaging (MRI).

Among 23 patients who were referred for this trial, 10 patients finally were included and received 3-6 cycles [ 177 Lu] Lu-PSMA therapy. No hematologic or renal toxicity was noted. Clinical improvement or stability was seen in 9/10 patients. The comparison of MRI before and after therapy revealed 3 patients with partial response, 4 patients with stable disease and 3 patients with progressive disease. Six-month and 1-year survival rates were 100% and 80% after first dose of [ 177 Lu] Lu-PSMA therapy.

This study demonstrated that [ 177 Lu] Lu-PSMA therapy could be a safe and potentially effective salvage therapy in the progressive/persistent GBM and should be more evaluated with further dedicated study to assess more precise selection criteria and therapeutic protocol and timing.