Study: CKD Patients Are At Greater Risk for Hematological Toxicities When Receiving 177Lu-Dotatate

Drug dose and monitoring should be individualized based on patients’ unique bone marrow health profile with their age, comorbidities, and prior marrow toxic drug use accounted for.

Despite dose adjustments, patients with chronic kidney disease (CKD) are at an increased risk of hematological toxicities and must have close laboratory follow-up when receiving 177Lu-dotatate for the treatment of metastatic neuroendocrine tumors (NETs), according to a presentation at the North American Neuroendocrine Tumor Society (NANETS) 2021 NET Medical Symposium.

Presenter Sandhya Manohar, MBBS, a nephrologist at Mayo Clinic, said CKD is common among patients with metastatic neuroendocrine tumors, although the novel therapy 177Lu-dotatate has not been widely studied in this patient population. In her research, Manohar studied experiences with peptide receptor radionuclide therapy (PRRT) and compared results for patients with and without CKD, including hematological, cancer, and renal outcomes.

In total, 86 patients were included in the study and divided into CKD and non-CKD groups. Among those with CKD, 48% were female, 97.4% were white, and all had received prior somatostatin-based therapy. One-third had received systemic chemotherapy or targeted therapy. Furthermore, comorbidities were common among both the CKD and non-CKD groups, especially hypertension and diabetes. Most patients were able to receive approximately 3 cycles of 177Lu-docatate, Manohar said.

According to the presentation, 4 patients had acute kidney injury and hypotension was the predominant etiology. Notably, none of these cases were attributed to the drug. Two patients had stage 3 CKD. One of those patients had a peak creatinine level of 1.8 mg/dl, although this stabilized and the patient was able to receive all 4 cycles of 177Lu-docatate and had stable disease at 6 months. The other patient had a much higher peak creatinine level at 2.62, and that patient died in a local facility approximately 1 month later.

When analyzing the nephrotoxicity results, Manohar noted a significant drop in kidney function at 3 months and 6 months post-treatment, with more significant decreases seen in the non-CKD group. However, she said these decreases were not as significant as would be expected, and the larger decline in the non-CKD patients could not be attributed to 177Lu-docatate. Unlike nephrotoxicity, platelet toxicity was more widespread in CKD patients, despite dose adjustments.

Interestingly, Manohar said 3 patients had CKD stage 4, and 177Lu-docatate was mainly given to these patients for palliative care. The first patient had excellent outcomes and is still alive, although the other 2 patients received fewer cycles. One patient was lost to follow-up so there is no available information about their outcomes, and the other patient died due to disease progression.

Based on these findings, Manohar said that patients with CKD are at a significantly increased risk for hematological toxicity and require close follow-up. Drug dose and monitoring should be individualized based on patients’ unique bone marrow health profile with their age, comorbidities, and prior marrow toxic drug use accounted for. The long-term impact of 177Lu-docatate on kidney function is still unclear and should be studied in future research, Manohar said.

REFERENCE

Manohar, S. 177Lu-docatate peptide receptor radionuclide therapy in chronic kidney disease patients: a single center experience. Presented at: North American Neuroendocrine Tumor Society (NANETS) 2021 NET Medical Symposium. November 5, 2021. Accessed November 5, 2021. https://nanetsvirtual2021.vfairs.com/en/hall