Characteristics and Outcomes of Therapy-Related Myeloid Neoplasms after Peptide Receptor Radionuclide/Chemoradionuclide Therapy (PRRT/PRCRT) for Metastatic Neuroendocrine Neoplasia: A Single Institutional Series

Abstract

Background: Peptide receptor radionuclide/chemoradionuclide therapy(PRRT/PRCRT) is an emerging therapy in patients with metastatic neuroendocrine neoplasia (NEN). However, therapy-related myeloid neoplasms (t-MN) remain a potential complication with substantial adverse outcomes. The study reviewed our PRRT/PRCRT patients who developed t-MN, with regard to their clinicopathological features and outcomes.

Methods: Retrospective analysis of all patients diagnosed with t-MN, defined as per revised 2016 WHO classification, from this single centre cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next generation sequencing using an in-house 26 gene panel were performed.

Findings: Twenty-five (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4 - 91). Twenty-two of 25 (88%) patients had Grade 1-2 pancreatic or small bowel NEN with moderate metastatic liver burden. The majority, 22 of 25 (88%) received concomitant radiosensitising chemotherapy. All 25 patients achieved disease stabilisation (68%) or at least a partial response (32%) on RECIST 1.1 assessment at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 x 109/L, range 3 - 75) and 17 (68%) were NEN progression free. Marrow genetic analysis revealed unfavourable karyotype in 16/25 (66%) patients and tumour protein 53 (TP53) mutations in nine (36%). Azacitidine therapy was utilised in ten eligible patients, while four received induction chemotherapy for AML. The median overall survival from the time of t-MN diagnosis was 13 months (range 1 - 56), with cause of death due largely to haematological disease progression.

Interpretation: The diagnosis of t-MN after PRRT/PRCRT is uncommon but a serious complication with poor overall survival. Most patients present with thrombocytopenia, unfavourable genetic mutations and poor response to t-MN treatment.

Funding: No funding source involved.

Declaration of Interest: RJH holds shares in Telix Pharmaceuticals on behalf of the Peter MacCallum Cancer Centre. MSH reports personal fees and non-financial support from Ipsen and Sanofi Genzyme, personal fees and other from Endocyte, outside the submitted work. All remaining authors declare no competing interests.

Ethical Approval: The study was approved by the hospital’s medical ethics committee as a retrospective audit with approval of waiver for patient consent (HREC Project number 18/61R). All patients had provided written, informed consent for PRRT/PRCRT.