Sept. 04, 2020
Lutetium Lu 177 dotatate, a peptide receptor radionuclide therapy (PRRT), is a tumor-targeted treatment that uses radiation to induce tumor cell death in neuroendocrine tumors (NETs) via β particle-emitting radionuclide linked to a somatostatin peptide analog.
Therapy-related myeloid neoplasm (t-MN) has been reported as a potential long-term and frequently lethal adverse event after PRRT.
Oncologists Mohamad (Bassam) B. Sonbol, M.D., at Mayo Clinic's Arizona campus, and Thorvardur (Thor) R. Halfdanarson, M.D., at Mayo Clinic's Minnesota campus, led a team that reviewed the literature to better understand the incidence of t-MN after PRRT.
A systematic review was conducted, and the results published online in JAMA Oncology in April 2020, consisting of 28 articles comprising 7,334 patients who were treated with peptide receptor radionuclide therapy for neuroendocrine tumors. The incidence of t-MN was variable between studies with mean incidence of 2.61%. Of all 134 cases of t-MN, cytogenetic abnormalities were reported in 32 patients with the most common abnormality being complex cytogenetics, consistent with t-MN following exposure to alkylating agents or irradiation.
The authors concluded that the risk of t-MN after peptide receptor radionuclide therapy is small but not insignificant given the poor prognosis after t-MN diagnosis. Close monitoring is warranted to identify such patients early in the disease course when hematologic abnormalities persist.
PRRT is an effective regimen for patients with NETs who express somatostatin receptors and one of the few treatment options that showed survival benefit in this patient population. Because many of these patients are experiencing longer survival, the question of long-term safety is important. Hematologic adverse events are common with about 25% of patients experiencing grade 1/2 thrombocytopenia along with anemia (14%) and neutropenia (4%). Although most of these adverse events are reversible, the authors confirmed that about 2.6% (95% CI, 0.99-4.23) of patients develop t-MN.
Counseling patients regarding the risk of t-MN is important because most of the reported cytogenetic abnormalities carry an adverse prognosis with a survival period of around 12 to 14 months after t-MN diagnosis. Therefore, oncologists should be vigilant and have a low threshold for investigating persistent cytopenia (especially thrombocytopenia) or unexplained macrocytosis, especially because most centers that offer PRRT are destination centers and patients are typically followed by their local oncologists in between and after treatments.
For patients who may have multiple treatment options such as patients with pancreatic NETs, it may be prudent to exhaust other options available and not known to result in t-MN such as everolimus and sunitinib prior to proceeding with PRRT. This may particularly apply to younger patients.
Unfortunately, t-MN remains a highly lethal malignancy. Future studies, especially prospective trials, should focus on studying potential risk factors for adverse events, especially molecular predictors of t-MN along with biomarkers that predict efficacy, which would help in selecting and personalizing treatments with maximum efficacy and less toxicity.
For more information
Sonbol MB, et al. Assessment of therapy-related myeloid neoplasms in patients with neuroendocrine tumors after peptide receptor radionuclide therapy: A systematic review. JAMA Oncology. 2020;6:1086.