Ibrutinib pharmacokinetics in B-lymphoproliferative disorders discloses exposure-related incidence of hypertension
Loïc Ysebaert, Caroline Protin, Lucie Obéric, Guillaume Beziat, Sandra De Barros, Baptiste Bonneau, Ben Allal, Malika Yakoubi, Anne Quillet-Mary, Fabien DespasObjective:
Ibrutinib has been the first Bruton tyrosine kinase inhibitor (BTKi) authorized for the treatment of B-cell lymphoproliferative disorders (B-LPDs). Numerous publications have confirmed the efficacy of this orally administrated drug in chemo-free regimens for B-LPDs. They also reported several adverse events (AE) associated with ibrutinib treatment. Whether these AEs depended on ibrutinib exposure has however been seldom explored.
Methods:
In the study reported here, the incidence of AE was recorded in 92 patients with B-LPD (mostly chronic lymphocytic leukemia
Results:
This PK evaluation was analyzed regarding AEs recorded over the first year of therapy, which were similar as in published reports. PK data disclosed a significant impact of ibrutinib exposure on infections but mostly on the occurrence of hypertension. The latter was mostly related to dihydrodiol-ibrutinib (DHD-ibrutinib) exposure.
Conclusions:
These data suggest that a DHD-ibrutinib assay after one month of treatment could be interesting to consider a lower dosage for patients above maximal concentration thresholds for the drug, its metabolite or the sum of both. Whether this can be applied to newer BTKi remains to be explored but it could be important for patients to whom ibrutinib is proposed.