Efficacité de l’éculizumab comme traitement de la microangiopathie thrombotique induite par la gemcitabine : à propos d’un cas

Thrombotic microangiopathy (TMA) is a rare but severe complication of tumors and their chemotherapeutic treatment. We report on two patients with chemotherapy-induced TMA who were successfully treated with a short course of the terminal complement inhibitor eculizumab. Both patients quickly achieved remission of microangiopathic hemolytic anemia and recovery of renal function. After withdrawal of eculizumab, remission was stable over an observation period of 47 months and 15 months, respectively. Our data show that eculizumab is effective in treating chemotherapy-induced TMA. Discontinuation of eculizumab is feasible once the complement-activating condition is controlled and the trigger is eliminated. Additional studies need to determine the optimal duration of complement-directed therapies and validate effective monitoring strategies after discontinuation of such therapy.

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“…In agreement with others we found that TPE/plasma infusion was not effective in patients with chemotherapy-induced TMA [12,13,14,15,16,17,18].…”

Section: Discussionsupporting

confidence: 93%

Eculizumab in chemotherapy-induced thrombotic microangiopathy

Schulte-Kemna

Reister

Bettac

et al. 2020

CNCS

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“…Which is supported in the study of Grall and al (4), by the deposits of C5b9 (membrane attack complex) found along the glomerular and tubular membrane and in the capillary wall on immuno uorescence in kidney biopsy. In this context, Eculizumab, a monoclonal antibody directed against complement protein C5 used in aHUS, has been used and seemed e cient in numerous case reports of G-TMA (5,(8)(9)(10)(11)(12)(13)(14)(15). The observational retrospective study of Grall and al (4) reported 12 cases of G-TMA treated by Eculizumab after Gemcitabine discontinuation with a median of 4 injections and 900 mg/injection.…”

Section: Discussionmentioning

confidence: 99%

Thrombotic microangiopathy after long lasting treatment by Gemcitabine: description, evolution and treatment of a rare case report

Bertin

Gauthier

Boullenger

et al. 2023

Preprint

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Background : Thrombotic microangiopathy is an uncommon but severe complication that may occur in cancer patients under Gemcitabine chemotherapy. Gemcitabine induced thrombotic microangiopathy can clinically and biologically present as atypical hemolytic uremic syndrome, with activation of the complement pathway asking the question of the use of Eculizumab. Case presentation : We describe here the case of a patient suffering from metastatic cholangiocarcinoma treated by Gemcitabine for 4 years leading to remission of the underlying neoplasia. Despite an impressive response to therapy, she developed thrombopenia, regenerative anemia and acute kidney injury leading to the suspicion then diagnosis based on renal biopsy of a very late Gemcitabine associated thrombotic microangiopathy. Spontaneous evolution after treatment interruption was favorable without dialysis requirement. However, in this case where Gemcitabine is the only chemotherapy remaining for a mortal underlying condition, we discussed re-initiation of Gemcitabine under Eculizumab treatment. Conclusions : This atypical case of thrombotic microangiopathy illustrates the importance of recognizing, even belatedly, this rare but serious complication of chemotherapy. It asks the question of resumption of discontinued chemotherapy notably under Eculizumab cover, in this population with high risk of cancer progression.

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“…Eculizumab has also been used in the management of GiTMA with significant improvement in both renal function and hematological parameters [5,[14][15][16][17]. It is often used for patients who are at high risk for complications such as thrombocytopenia, progressive renal failure, or extrarenal complications such as abnormal vascular permeability.…”

Section: Discussionmentioning

confidence: 99%