Drug Induced Thrombotic Microangiopathy in Cancer Patients: A Clinicopathologic Series

Drug-induced thrombotic microangiopathy (TMA) is a major sequela of cancer therapies. The diagnosis of drug-induced TMA is often presumptive, making accurate clinical characterization difficult.

We retrospectively reviewed clinical presentation and outcomes of 53 patients with biopsy-proven renal TMA due to cancer therapies in a cancer center between 2001 and 2023.

Median age at presentation was 64 (44-81) years and our cohort was 72% (38/53) female. Most common malignancies treated were pancreatic (19%), breast (17%), ovarian (15%) and lung cancer (15%). Forty-one patients (77%) presented with acute kidney injury (AKI), out of which nine patients (17%) required dialysis. Most common implicated drugs were gemcitabine (51%), bevacizumab (25%), doxorubicin (15%), and various tyrosine kinase inhibitors (19%) including epidermal growth factor receptor blocker erlotinib (4%). Cessation of the offending drug was the mainstay of management in 51 patients (96%); other treatment strategies included steroid (15%) and eculizumab (8%). After median follow-up of 4 (1.1-7.1) years, median overall survival was 2.1 years and median kidney failure-free survival was 1.8 years. Among patients with AKI, 16 patients (39%) had kidney recovery within a year. One out of nine patients requiring dialysis was weaned off within a year. Older age, lower glomerular filtration rate at presentation and thrombocytopenia were associated with worse kidney prognosis. Chronic TMA was noted upon kidney biopsy in most patients (85%). Pathologic findings associated with worse kidney outcome were the presence of microvascular thrombi and endothelial swelling.

Though limited by its retrospective nature, our study suggests that doxorubicin and erlotinib are underrecognized causes of drug-induced TMA. Many patients' biopsies had chronic changes in glomeruli, arterioles, as well as small arteries, indicating that mild, ongoing endothelial injury is present before development of overt TMA. Clinical vigilance with early cessation of offending drug may help kidney recovery.