Drug-Induced Thrombotic Microangiopathy in Patients with Cancer : A Clinicopathologic Series

Gemcitabine, bevacizumab, and doxorubicin were the most common drugs implicated in drug-induced thrombotic microangiopathy in cancer. Cessation of the offending drug was the mainstay of management. The median overall survival was 2.1 years, and the median kidney failure‑free survival was 1.8 years after biopsy-confirmed diagnosis.

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 (15%) cancers. Forty-one patients (77%) presented with AKI, 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 EGF receptor blocker erlotinib (4%). Cessation of the offending drug was the mainstay of management in 51 patients (96%); other treatment strategies included steroids (15%) and eculizumab (8%). After a median follow-up of 4 years (1.1-7.1), 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 of nine patients requiring dialysis was weaned off within a year. Older age, lower GFR at presentation, and thrombocytopenia were associated with worse kidney prognosis. Chronic TMA was noted upon kidney biopsy in most of the patients (85%). Pathologic findings associated with worse kidney outcome were the presence of microvascular thrombi and endothelial swelling.

Although 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, and small arteries, indicating that mild, ongoing endothelial injury is present before the development of overt TMA. Clinical vigilance with early cessation of the offending drug may help kidney recovery.