Vorasidenib liver toxicity and Gilbert’s syndrome
I’m currently taking Vorasidenib/Voranigo for an IDH1-mutant diffuse astrocytoma, WHO grade 2.
I started at the standard dose of 40 mg daily, but had to pause treatment because my liver enzymes increased significantly. The pause lasted about seven weeks. My highest values were roughly AST/GOT 120 U/L and ALT/GPT 226 U/L. After stopping Vorasidenib, the values improved only gradually and somewhat unevenly, but eventually recovered enough for me to restart at a reduced dose of 20 mg daily.
I also have genetically confirmed Gilbert’s syndrome / Morbus Meulengracht. My oncologist suspects this may be relevant, especially regarding the bilirubin issue and possibly the slower recovery, although Gilbert’s syndrome alone would not usually explain marked ALT/AST elevations.
I contacted Servier and was told that in the pivotal trial there was one patient with Gilbert’s syndrome in the Vorasidenib group, and that this patient had a grade 4 transaminase elevation.
I’d be very interested in hearing from others who had liver enzyme elevations on Vorasidenib:
Did anyone here have to pause Vorasidenib because of liver values and then restart at a lower dose, such as 20 mg or 10 mg?
If so, were you able to stay on it long-term?
Did your liver enzymes stabilize after the dose reduction, or did they rise again?
Was anyone later able to return to the full 40 mg dose?
And has anyone else with Gilbert’s syndrome taken Vorasidenib?
I’d be grateful for any experiences, especially regarding what happened over the following weeks and months after restarting.