This study aims to retrospectively assess the safety of [225Ac]Ac-PSMA-PRLT, both as monotherapy and in combination (TANDEM) with Lutetium-177, concerning tolerance after the radiopharmaceutical administration and long-term safety, its impact on salivary glands' function, overall survival (OS), and follow-up duration. Between December 2020 and September 2024, 89 patients received a total of 151 cycles of [225Ac]Ac-PSMA-PRLT. Patients with at least one follow-up (n = 71) were included in the analysis to evaluate xerostomia, as well as long-term hematological, renal, and hepatic toxicities, graded according to CTCAE v5.0. The most common adverse event after the radiopharmaceutical administration was flare pain (n = 16). As of the time of analysis, 68 patients had passed away (76.4%; range of survival 5 days to 39 months, median 7 months), while 21 patients were still alive (23.6%; follow-up duration: 1-33 months). Severe (G3/G4) long-term adverse events were rare, with 15 cases of G3 anemia (21.1%), 6 cases of G3 leukocytopenia (8.4%), and 14 cases of G3/G4 thrombocytopenia (19.7%). Hematological toxicity was primarily associated with severe bone marrow involvement or prior chemotherapy. Additionally, one case of G3 nephrotoxicity (1.4%) and six cases of G3 hepatotoxicity (8.4%) were observed. Only nine patients (12.7%) reported de novo xerostomia (G1/G2). In conclusion, this study demonstrates that [225Ac]Ac-PSMA PRLT, both as monotherapy and combined with [177Lu]Lu-PSMA as TANDEM PRLT, is generally safe in terms of both tolerance after the radiopharmaceutical administration and long-term toxicity.
Cancers. 2025 Jan 26*** epublish ***
Elisabetta Perrone, Alessandro Giordano, Maria Lucia Calcagni, Lucia Leccisotti, Roberto Moretti, Aleksandr Eismant, Kriti Ghai, Tanay Parkar, Aditi Mishra, Axel Heidenreich, Ralph M Wirtz, Jörg Müller, Lukas Greifenstein, Richard P Baum
CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany., Institute of Nuclear Medicine, Università Cattolica del Sacro Cuore, 00168 Rome, Italy., Unità della Fisica per le Scienze della Vita, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy., Department of Urology, Uro-Oncology, Robot-Assisted and Reconstructive Surgery, Faculty of Medicine, University of Cologne, University Hospital Cologne, 50937 Cologne, Germany., Institute of Pathology, St. Elisabeth Hospital Köln-Hohenlind, 50935 Cologne, Germany., Department of Neurology, Vivantes Klinikum Spandau, Charité-Universitätsmedizin, 10117 Berlin, Germany.