Thématique :
- Foie
Originalité :
Solidité :
Très solide
Doit faire évoluer notre pratique :
Dans certains cas
Nom du veilleur :
Professeur Christine SILVAIN
Coup de coeur :
  2019 Feb;69(2):831-844.  
  doi: 10.1002/hep.30222.  
  Liver Complications Following Treatment of Hematologic Malignancy With Anti-CD22-Calicheamicin (Inotuzumab Ozogamicin).  
  McDonald GB, Freston JW, Boyer JL, DeLeve LD  


Treatment of hematological malignancy with antibody-drug conjugates (ADCs) may cause liver injury. ADCs deliver a toxic moiety into antigen-expressing tumor cells, but may also injure hepatic sinusoids (sinusoidal obstruction syndrome; SOS). We studied patients who received an anti-CD22/calicheamicin conjugate (inotuzumab ozogamicin; InO) to gain insight into mechanisms of sinusoidal injury, given that there are no CD22+ cells in the normal liver, but nonspecific uptake of ADCs by liver sinusoidal endothelial cells (LSECs). Six hundred thirty-eight patients (307 with acute lymphocytic leukemia [ALL], 311 with non-Hodgkin's lymphoma [NHL]) were randomized to either InO or standard chemotherapy (controls). While blinded to treatment assignment, we reviewed all cases with hepatobiliary complications to adjudicate the causes. Frequency of SOS among patients who received InO was 5 of 328 (1.5%), compared to no cases among 310 control patients. Drug-induced liver injury (DILI) developed in 26 (7.9%) InO recipients and 3 (1%) controls. Intrahepatic cholestasis (IHC) was observed in 4.9% of InO recipients and in 5.5% of controls. Subsequent to the randomization study, 113 patients with ALL underwent allogeneic hematopoietic cell transplantation (HCT); frequency of SOS in those previously exposed to InO was 21 of 79 (27%) versus 3 of 34 (9%) in controls. An exploratory multivariate model identified a past history of liver disease and thrombocytopenia before conditioning therapyas dominant risk factors for SOS after transplant.

Conclusion: Frequencies of SOS and DILI after inotuzumab ozogamicin treatment were 1.5% and 7.9%, respectively, compared to none and 1% among controls who received standard chemotherapy. These data suggest that ADCs that do not target antigens present in the normal liver have a relatively low frequency of SOS, but a relatively high frequency of DILI.

Question posée
Fréquence de l’hépatotoxicité (DILI) et des syndromes d’obstruction sinoïdale (SOS) induits par les conjugués anti-CD22/calicheamicine (inotuzumab ozogamicin; InO) utilisés dans les chimiothérapie de patients avec leucémie aiguë lymphoblastique ou des lymphomes non hodgkiniens.
Question posée
Les fréquences de SOS and DILI après traitement par InO étaient de 1,5% et 7,9%, respectivement, comparées à 0% et 1% chez les patients contrôles qui avaient reçu une chimiothérapie standard.

A savoir.