Dataset Information

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

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.

SUBMITTER: Grall M

PROVIDER: S-EPMC8293501 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTreatment with proteasome inhibitors like carfilzomib in patients with multiple myeloma (MM) can induce thrombotic microangiopathy (TMA) characterized by neurological symptoms, acute kidney injury, hemolysis and thrombocytopenia. Successful treatment with the monoclonal antibody eculizumab was described for these patients, but reports of ideal management and definitive treatment protocols are lacking.Case presentationThe first case describes a 43-years-old IgG-kappa-MM patient that developed TMA during the first course of carfilzomib-lenalidomide-dexamethasone (KRd) consolidation after autologous stem cell transplantation (ASCT). In the second case, a 59-years-old IgG-kappa-MM patient showed late-onset TMA during the fourth and last cycle of elotuzumab-KRd consolidation within the DSMM XVII study of the German study group MM (DSMM; clinicalTrials.gov Identifier: NCT03948035). Concurrently, he suffered from influenza A/B infection. Both patients had a high TMA-index for a poor prognosis of TMA. Therapeutically, in both patients plasma exchange (TPE) was initiated as soon as TMA was diagnosed. In patient #1, dialysis became necessary. For both patients, only when the complement inhibitor eculizumab was administered, kidney function and blood values impressively improved.ConclusionIn this small case series, two patients with MM developed TMA due to carfilzomib treatment (CFZ-TMA), the second patient as a late-onset form. Even though TMA could have been elicited by influenza in the second patient and occurred after ASCT in both patients, with cases of TMA post-transplantation in MM being described, a relation of TMA and carfilzomib treatment was most likely. In both patients, treatment with eculizumab over two months efficiently treated TMA without recurrence and with both patients remaining responsive months after TMA onset. Taken together, we describe two cases of TMA in MM patients on carfilzomib-combination treatment, showing similar courses of this severe adverse reaction, with good responses to two months of eculizumab treatment.