What To Know About Vorasidenib Side Effects
- For patients facing low-grade glioma, the targeted drug vorasidenib has emerged as a milestone treatment option. It is the first systemic therapy specifically for people with certain gliomas with mutations in the IDH1 or IDH2 genes.
- The drug is generally considered well-tolerated, but because it is new, there is no long-term data on side effects that might develop down the line.
- For example, because the drug influences metabolic and epigenetic processes (via inhibiting mutant IDH), there’s a theoretical possibility that long-term treatment might have unforeseen effects: such as on normal brain cells, metabolism, or other systems.
- The official prescribing information also notes that vorasidenib may affect fertility in both men and women.
- The most commonly reported side effects are often manageable, and include fatigue, headache, gastrointestinal symptoms, and muscle, joint, or bone pain.
“There are many unknowns about vorasidenib and some things we do know a little bit about because of the clinical trials that have been performed,” Dr. Sylvia Kurz, neuro-oncologist at Yale School of Medicine, tells SurvivorNet.
Read More- Will tumors eventually progress despite treatment?
- When they do, will vorasidenib exposure change the tumor’s behavior?
- Will prognosis or treatment options change after progression?
Potential Side Effects & Reproductive Risks
Because the drug influences metabolic and epigenetic processes (via inhibiting mutant IDH), there’s a theoretical possibility that long-term treatment might have unforeseen effects: such as on normal brain cells, metabolism, or other systems. As of now, no clear “smoking gun” for such effects has emerged, but that does not mean it can’t emerge later on.
“For most patients, this is really fairly well tolerated medication and I think that gives us confidence. We do not suspect, but we do honestly not know if there are any long-term consequences from vorasidenib,” Dr. Kurz explains.
The official prescribing information notes that vorasidenib may affect fertility in both men and women. For people of childbearing age, this raises difficult choices and many questions remain unanswered about the extent, duration, and reversibility of those effects, and about safer ways to preserve fertility.
“I have several patients who have chosen not be on vorasidenib, who I thought would be really great candidates for it. But they have not chosen that pathway because they wanted to have more children,” Dr. Kathryn Nevel, neuro-oncologist at Indiana University, told SurvivorNet in a previous conversation.
Known Side Effects of Vorasidenib
Many people tolerate vorasidenib reasonably well, but there are some side effects that doctors are aware of.
Common effects include:
- Fatigue (tiredness and lack of energy)
- Headache
- Gastrointestinal symptoms (diarrhea, nausea, abdominal discomfort)
- Muscle, joint or bone pain
- Reduced appetite, stomach upset
Importantly: many of these side effects are manageable. According to a patient- and caregiver-oriented information sheet on vorasidenib, most side effects are described as “mild to moderate,” and often reversible or controllable — especially compared to what many experience during traditional chemotherapy.
Because vorasidenib is taken daily, and often long-term (until the tumor progresses or side effects become intolerable), the dosing regimen matters. Patients are typically monitored with blood tests, especially liver enzymes, before treatment and periodically during therapy (often every two weeks in the first two months).
Liver Damage
One of vorasidenib’s more worrisome side effects is laboratory abnormalities or liver-related adverse events.
“The main concern is that patients may have a rise in their liver function tests,” Dr. Kurz explains. “Sometimes people kind of talk a little bit about dizziness or feeling woozy after taking the drug, but these are overall kind of considered minor side effects. In a few cases, people have observed more extreme rises in the liver function and tests that we see on the lab … and in a few patients they have to discontinue treatment for that reason,” she adds.
Elevated liver enzymes (increased levels of ALT, AST, GGT) have been among the most frequent lab abnormalities. In some cases, these elevations reach grade 3 or 4 (i.e., more severe). In the INDIGO trial, about 9.6% of patients on vorasidenib experienced a grade-3 or higher increase in ALT (a liver enzyme).
Elevations in liver enzymes are usually reversible, but in some circumstances could signal liver stress or toxicity. Patients are advised to alert their care team if they have signs such as yellowing of skin or eyes (jaundice), dark urine, upper-right abdominal pain, loss of appetite, or unusual fatigue.
Because of that risk, regular blood-work monitoring is strongly recommended.
Neurological & Other Serious Side Effects
Because vorasidenib is a brain-penetrant drug (designed to cross the blood-brain barrier) neurological effects are a particular concern.
These might include:
- Seizures (named as a possible, though less common side effect)
- Dizziness (in some cases, patients report dizziness or other neurological symptoms)
Other less common or rarer effects are insomnia, tinnitus or “otoacoustic perception” (hearing sounds), abdominal pain, changes in electrolytes (dyselectrolytemia), and anemia.
It is worth noting, though, that despite these risks, Dr. Kurz and other specialists consider vorasidenib “generally well tolerated.”
“We do think vorasidenib is quite well tolerated. Side effects are not a big concern,” Dr. Kurz explains. “And I think even over this past year or two when we used it more regularly in real world patients, there were no major side effects detected.”
Questions To Ask Your Doctor
- Am I a candidate for vorasidenib now and do you recommend it?
- Am I a candidate for a watch-and-wait approach instead?
- What are the benefits of starting early versus delaying treatment?
- Are there any medical conditions I have that make vorasidenib riskier?
- What side effects should I expect, and how will they be monitored?
- How often will I need bloodwork or imaging while on treatment?
Learn more about SurvivorNet's rigorous medical review process.
