Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre

François Provot,Jean-Philippe Coindre,Florence Daviet,Noémie Jourde Chiche,Maximilien Grall,Claire Pouteil-Noble,Paul Coppo,Steven Grangé,Ygal Benhamou,Dominique Guerrot,Alexandre Karras,Arnaud François,Véronique Frémeaux-Bacchi,Claire Presne,Agnès Veyradier

doi:10.1186/s12882-021-02470-3

Abstract

BackgroundGemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA).MethodsThis study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016.ResultsTwelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4–44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2–22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0–10) before treatment vs 0 (range 0–1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group.ConclusionsThese results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.

Highlights

Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA)
Single reports suggested the efficacy of eculizumab in gemcitabineinduced TMA (G-TMA) [11], a monoclonal antibody directed against the complement protein C5 that has been approved for treatment of atypical hemolytic uremic syndrome (HUS)
The present study evaluated the efficacy of eculizumab in a retrospective series of patients with G-TMA

Summary

Introduction

Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). Thrombotic microangiopathy (TMA) syndromes are characterized by a microangiopathic hemolytic anemia, peripheral thrombocytopenia, and organ injury of variable severity [1]. The principal subtypes of TMA are thrombotic thrombocytopenic purpura (TTP) mainly due to anti-ADAMTS13 autoantibodies and the hemolytic uremic syndrome (HUS) associated with shigatoxin-related endothelial toxicity (shiga-toxin related HUS) or with complement alternative pathway dysregulation (atypical HUS or aHUS). Single reports suggested the efficacy of eculizumab in G-TMA [11], a monoclonal antibody directed against the complement protein C5 that has been approved for treatment of atypical HUS. In this context, the present study evaluated the efficacy of eculizumab in a retrospective series of patients with G-TMA

Methods

Results

Conclusion