Abstract: SA-PO260
Successful Treatment of Refractory Gemcitabine-Associated Thrombotic Microangiopathy with Eculizumab
Session Information
- Trainee Case Reports - VI
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Shimonov, Daniil, NYU-Winthrop Hospital, Mineola, New York, United States
- Friedman, Naomi, Stony Brook School of Medicine, Bronx, New York, United States
- Khatri, Minesh, NYU-Winthrop Hospital, Mineola, New York, United States
Introduction
Gemcitabine can lead to thrombotic microangiopathy (TMA) which is characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and AKI. We report a novel treatment approach for a man with pancreatic carcinoma with refractory gemcitabine associated TMA successfully treated with eculizumab, a monoclonal antibody against C5 complement.
Case Description
A 69-year-old man with a history of pancreatic adenocarcinoma treated with gemcitabine and normal baseline renal function (Cr 1.0mg/dl) presented with thrombocytopenia (platelets 31 K/uL), MAHA (schistocytes and LDH 582 IU/L), and AKI (Cr 2.1mg/dl) concerning for Gemcitabine-associated Thrombotic Microangiopathy (GA-TMA), subsequently diagnosed by renal biopsy. Initially, chemotherapy was held and patient was started on high dose glucocorticoids and 20 PLEX treatments, with rituximab added the next month due to ongoing TMA. There was mild improvement in renal function, but hemolysis and thrombocytopenia persisted, prompting implementation of eculizumab a month later. Patient's hematologic parameters improved and kidney function stabilized. In the meantime, chemotherapy was delayed for 5 months, his cancer progressed, and he passed away 7 months after presentation.
Discussion
This case report demonstrated that eculizumab could successfully treat refractory GA-TMA. GA-TMA is a rare condition that carries mortality rates from 50-70%. Discontinuing gemcitabine, initiating steroids, PLEX, dialysis, and rituximab have been standard therapy. Eculizumab has been shown in a few case reports to normalize some or all the parameters of the disorder, indicating that dysregulation of the complement pathway may play a significant role. Our patient did not respond well to steroids, PLEX and rituximab prompting a novel approach with eculizumab, with subsequent significant improvement in the hemolytic parameters and stabilization of renal function. Further research should focus on randomized controlled trials comparing eculizumab with standard therapy for GA-TMA, and potentially as first line therapy to possibly allow for earlier initiation of non-Gemcitabine chemotherapeutic agents. We need an improved understanding of the mechanisms by which certain chemotherapeutic agents induce TMA, and be able to better identify patients that would be most likely to benefit from eculizumab.