Radioimmunotherapy-associated myeloid neoplasms: Real-world multicenter retrospective study using TriNetX database.

Abstract

12043 Background: Radioimmunotherapy (RIT) utilizing monoclonal antibodies conjugated with therapeutic radionuclides, has emerged as a promising treatment option in oncology. While demonstrating significant clinical efficacy, concerns regarding therapy-related myeloid neoplasms (t-MNs) have been raised in other contexts, particularly following RIT for non-Hodgkin lymphoma. This study aims to investigate the risk of t-MNs following treatment with Lutathera (177Lu-DOTATATE) and Pluvicto (177Lu-PSMA-617) in patients with neuroendocrine tumors and metastatic castration-resistant prostate cancer. Methods: We conducted a multicenter retrospective study using the TrinetX database network, a federated Electronic Medical Record Network including adult patients with a history of using Lutathera and/or Pluvicto and developed t-MNs. Statistical analysis is performed on the TrinetX research platform. Outcome analysis was performed for 1) Incidence of t-MNs. 2) Mortality rates and Survival analysis. Results: A total of 2370 patients who received either Lutathera (n=1368; 57.7%) or Pluvicto (n=1002; 42.3%) were identified in the database. Mean age was 71 years (±11 years), 64.98% (n=1540) were males and 70.08% were whites. Of the 2370 patients, 1.6% (n=39) developed t-MNs (26 MDS (1.09%), 13 AML (0.54%). Among these, 27 were in the Lutathera cohort (1.97% of total patients), and 12 were in the Pluvicto cohort (1.12%). The mean age in the t-MN cohort was 72 years (±9 years) and 50% were males. 16 (41%) patients with t-MN had prior chemo or radiotherapy. The remaining 23 patients (59%) received no anticancer therapy associated with t-MNs. Median survival for patients with t-MNs was 38.1 months, with an overall mortality of 51.2% at median follow-up. Conclusions: This is the largest study reporting the incidence of t-MN associated with RIT. Our study demonstrated a significant risk of therapy-related t-MNs following RIT, even in patients who did not receive additional chemoradiotherapy. Given the short follow-up, we hypothesize that the risk may increase with longer-term follow-up. Using this real-world data, our Next step would be to include Next-Generation Sequencing for further characterization of the genomic landscape of these patients. Demographic, treatment, and follow-up data of the study population. Baseline characteristics RIT RIT with t-MNs Total patients 2370 39 Mean age (in years) (SD) 71 (±11) 72 (±9) Gender*(%)MalesFemales 64.9822.07 50.046.6 Race*(%)WhitesAfrican American 70.087.60 73.338.6 Radiation therapy (%)Chemotherapy (%)CabazitaxelDocetaxelCarboplatinCisplatinDoxorubicinOlaparib 20.2-5.2016.70.730.220.765.0 41.0 Median follow-up (in months) 11.4 27.3 Median survival (in months) (IQR) 44.5 (41.6-48.3) 38.1 (15-51.6) Mortality rates (%) 28.9 51.2 *Indicates remaining Unknown/Other; IQR: Interquartile range.