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

BMC Nephrol. 2021 Jul 21;22(1):267. doi: 10.1186/s12882-021-02470-3.

Abstract

Background: Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA).

Methods: This 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.

Results: Twelve 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.

Conclusions: These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.

Keywords: Coagulation, thrombotic disorders and therapies, Cancer and thrombosis; Eculizumab; Gemcitabine-induced thrombotic microangiopathy.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Acute Kidney Injury* / complications
  • Acute Kidney Injury* / diagnosis
  • Acute Kidney Injury* / therapy
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Blood Transfusion / methods
  • Blood Transfusion / statistics & numerical data
  • Complement Inactivating Agents / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • France / epidemiology
  • Humans
  • Kidney Function Tests / methods
  • Male
  • Middle Aged
  • Recovery of Function
  • Remission Induction / methods
  • Renal Replacement Therapy / methods
  • Thrombotic Microangiopathies* / diagnosis
  • Thrombotic Microangiopathies* / etiology
  • Thrombotic Microangiopathies* / therapy
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic
  • Complement Inactivating Agents
  • Deoxycytidine
  • eculizumab
  • gemcitabine