Abstract: SA-PO216
Rechallenging Gemcitabine with Eculizumab in a Patient with Gemcitabine-Induced Thrombotic Microangiopathy
Session Information
- Onconephrology: Immunological Cross-Talk
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Sharma, Purva D., Northwell Health, New Hyde Park, New York, United States
- Hadji, Nerihan, Northwell Health, New Hyde Park, New York, United States
- Nimkar, Abhishek, Northwell Health, New Hyde Park, New York, United States
Introduction
Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage kidney disease. The mainstay of management is withdrawal of the offending drug and supportive care. Furthermore, a C5 inhibitor, eculizumab, has been successfully used in the treatment of GiTMA.
Case Description
A 78-year-old lady with a history of ovarian adenocarcinoma stage 4 on gemcitabine was referred for abnormal kidney function. She had CKD with a baseline serum creatinine (Scr) of 1.6-1.8 mg/dl. On this presentation, she had new onset hypertension and Scr was elevated to 2.8mg/dl. Hemoglobin was 8.7 mg/dl with elevated serum lactate dehydrogenase (539 U/L) and low haptoglobin (<20mg/dl). Urine analysis showed moderate proteinuria and hematuria with 30RBCs/HPF. Her spot urine protein-creatinine ratio (UPCR) was elevated at 1.5. A kidney biopsy was pursued which showed chronic thrombotic microangiopathy with severe glomerular capillary wall remodeling, 20% global glomerulosclerosis. Work up for causes of TMA was done including ADAMTS-13 level, antinuclear antibody level, HIV, direct antiglobulin levels, serum complement 3, serum complement 4, anti-neutrophilic cytoplasmic antibody levels and atypical HUS panel which came back unremarkable. Gemcitabine was thought to be the culprit medication and was withheld. Scr did not improve and the patient was initiated on eculizumab with an improvement in Scr to 2mg/dl. After a multidisciplinary discussion with oncology and the family, and based on the premise that gemcitabine was the only drug working for adenocarcinoma, it was decided to re-challenge Gemcitabine concurrently with eculizumab therapy. 3 months follow up showed Scr stable at 1.8mg/dl, normal LDH, Haptoglobin and a UPCR at 0.1.
Discussion
TMA secondary to Gemcitabine therapy is a rare condition. Physicians should have a high index of suspicion to diagnose GiTMA early in the course of the disease. Mainstay of management is discontinuation of gemcitabine and supportive care. Eculizumab has been tried in GiTMA with great success in improving hematologic and kidney parameters. However, continuation of Gemcitabine along with Eculizumab therapy is a novel strategy that has limited data. Further research is needed to validate this strategy.