At the 2017 ASH Annual Meeting, Dr. Brian Koffman interviewed Dr. Jennifer Brown from Dana Farber Cancer Institute at Harvard University in Boston regarding the association between idelalisib and liver inflammation seen in patients treated for their chronic lymphocytic leukemia (CLL).
Idelalisib is a selective phosphoinositide 3-kinase (PI3K) inhibitor approved in combination with rituximab in patients with relapsed CLL. PI3K is expressed in normal and CLL cells and inhibition of PI3K blocks a part of B cell signaling resulting in apoptosis (cell death). For more information on idelalisib, please see this article by Tom Henry, a CLL patient and pharmacist.
One adverse event associated with idelalisib is increased liver enzymes, suggesting liver inflammation, possibly due to an immune system reaction. A small study demonstrated that liver inflammation was more common in younger patients and those with the mutated IgVH type of CLL. Dr. Dr. Brown then looked at data from 6 large clinical trials to confirm these results which she presented at ASH 2017.
Take away Points:
- 853 patients were treated with idelalisib
- Patients included those that were treatment-naïve and those with relapsed/refractory CLL
- These 6 studies included treatment with idelalisib monotherapy, in combination with rituximab, in combination with bendamustine/rituximab, or in combination with obinutuzumab.
- Treatment-naïve patients with 17P deletion were also at greater risk of reversible transaminase elevation, but may be attributed to a study-related effect
- Results indicate liver inflammation was more common in treatment-naïve patients and was increased in younger patients
Idelalisib is a PI3K inhibitor that functions to increase CLL cell death; however, liver inflammation has been noted in some subgroups of patients including those that are younger and treatment naïve. These results have led to the hypothesis that liver inflammation is more common in patients with intact immune systems. Idelalisib may somehow increase autoimmune activity. Additional studies are necessary to confirm this. Importantly, patients should be monitored regularly for increases in liver enzyme levels.
Here is the link to the ASH abstract:
Risk Factors for Grade 3/4 Transaminase Elevation in Patients with Chronic Lymphocytic Leukemia Treated with Idelalisib
You can watch my interview with Dr. Brown below, or read the transcript here.
Joanne Faysal 4-24-18