What IDH Status Means for Glioma Treatment
- IDH (isocitrate dehydrogenase) is an enzyme that helps cells make energy. When the gene that makes IDH is mutated, it can cause abnormal cell growth, Dr. Jacob Mandel, a neuro-oncologist at Baylor College of Medicine, tells SurvivorNet.
- Doctors use IDH status to sort the most common adult gliomas into three types: astrocytoma (IDH-mutant), oligodendroglioma (IDH-mutant with a 1p/19q deletion), and glioblastoma, an IDH-wildtype, aggressive grade 4 tumor.
- Identifying a glioma’s type helps guide how aggressive treatment should be. IDH-mutant gliomas generally grow slower and have a better outlook.
- In 2024, the FDA approved vorasidenib (Voranigo), a targeted therapy for certain grade 2 IDH-mutant gliomas after surgery.
- The standard IDH test can miss less common mutations. If your report says there’s no IDH mutation, ask about getting genetic sequencing.
A glioma is a tumor that starts in the glial cells. These cells support and protect the nerve cells in your brain. There are several kinds of glioma. In adults, testing for IDH is one of the main ways doctors tell them apart.
Read MoreDetermining whether glioma has an IDH mutation helps doctors determine the best treatment approach.
Why IDH Status Matters in Glioma
Doctors use IDH, along with a few other tumor features, to classify the most common types of gliomas in adults.
The types of glioma include:
- Astrocytoma: Astrocytes are glial cells, and astrocytomas are tumors that develop from these cells. “For an astrocytoma, you typically will just have the IDH mutation,” Dr. Mandel explains.
- Oligodendroglioma: These tumors have the IDH mutation too, but they develop in a different type of glial cell, oligodendrocytes. They also have “a second mutation called a 1p/19q chromosomal deletion,” Dr. Mandel explains. Chromosomes are the packages that hold your DNA. In this deletion, the tumor cells are missing part of chromosome 1 and part of chromosome 19.
- Glioblastoma, IDH-wildtype. “Unfortunately, there is also a third type of glioma, which does not have an IDH mutation, which is called a glioblastoma, IDH-wildtype,” he says. “Wildtype” means the IDH gene is normal, with no mutation. Glioblastomas are “very aggressive, grade four type tumors that we often see, unfortunately, in older adults,” Dr. Mandel adds.
A tumor’s grade, from 1 to 4, describes how fast it’s likely to grow. Grade 4 is the fastest.
Astrocytomas can be grade 2, 3 or 4, while oligodendrogliomas are grade 2 or 3.
Why Your Type of Glioma Matters
Identifying the type of glioma a patient has can help doctors understand how it’s likely to behave and what treatment path to recommend.
“These classifications are very important because they really give you a different idea of what to expect as far as the patient’s prognosis,” Dr. Mandel says. Prognosis means the likely course of the disease. The type also guides “what’s the best treatment for these patients and how aggressive to be with these different treatments,” he adds.
In general, gliomas with an IDH mutation tend to grow slower and have a better outlook than IDH-wildtype glioblastoma.
Your own situation also depends on your tumor’s grade, its location, your overall health and other factors. Your care team can explain what applies to you.
IDH-mutant tumors now have a treatment that targets the mutation directly. In August 2024, the FDA approved vorasidenib (brand name Voranigo). It’s approved for people 12 and older with grade 2 astrocytoma or oligodendroglioma that has an IDH1 or IDH2 mutation after surgery.
Vorasidenib is a targeted therapy, a drug designed to block a specific change in cancer cells.
Testing for IDH
IDH testing usually starts with immunohistochemistry. This lab test uses a special stain to look for the mutated IDH protein in a tumor sample.
The stain is useful, but it isn’t perfect. It’s designed to catch the most common IDH mutation, and less common ones can slip by.
“We don’t always pick up all the different… mutations by doing that,” Dr. Mandel says.
That’s why doctors look harder in some cases, including in patients who are younger or in tumors that don’t “enhance,” or light up on an MRI scan, he adds.
Genetic sequencing, a lab test that reads the tumor’s genes directly, might be done in these cases.
If your report says there’s no IDH mutation, it’s reasonable to ask, “Was my tumor also checked with genetic sequencing?”
The answer can change your diagnosis and your treatment options.
Questions To Ask Your Doctor
- Has my tumor been tested for an IDH mutation?
- Do I need to undergo genetic sequencing as well?
- How is my glioma classified and what does that mean for treatment?
- Am I a candidate for targeted therapy?
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