Researchers are developing and testing new treatments for isocitrate dehydrogenase (IDH)-mutant gliomas, including targeted therapies and immunotherapies. These treatments may help improve survival rates or quality of life.

A glioma tumor may develop when glial cells in your brain or spinal cord have gene changes that cause the cells to grow and divide more quickly than usual. Multiple types of gene changes may cause glial cells to grow into tumors.

IDH-mutant gliomas have changes in the IDH1 or IDH2 gene. These genes instruct your body to produce isocitrate dehydrogenase (IDH) enzymes, which help release energy for cells to use.

If you have an IDH-mutant glioma, the tumor cells release an IDH enzyme that doesn’t work as it should. The mutant enzyme produces D-2 hydroxyglutarate (D-2HG) — a molecule that encourages tumor growth.

Types of IDH-mutant gliomas include IDH-mutant astrocytomas and oligodendrogliomas.

Conventional treatments for IDH-mutant gliomas include:

  • surgery
  • radiation therapy
  • chemotherapy

New and emerging treatments for IDH-mutant gliomas include:

  • targeted therapies, which target specific changes in cancer cells that help them grow and spread
  • immunotherapies, which help your immune system recognize and attack tumor cells

The Food and Drug Administration (FDA) has approved vorasidenib (Voranigo) as the first targeted therapy for IDH-mutant gliomas. This medication is a type of IDH inhibitor.

Researchers are also conducting clinical trials to test other types of IDH inhibitors, other targeted therapies, and immunotherapies for treating certain types of IDH-mutant gliomas.

Read on to learn about these new and emerging treatments.

IDH inhibitors are targeted therapies that block the production of D-2HG to slow or stop IDH-mutant tumor growth.

The FDA has approved the IDH inhibitor vorasidenib for use in adults and children ages 12 years and older who have undergone surgery to treat a grade 2 IDH-mutant glioma.

It’s possible that the FDA might approve vorasidenib for other groups of people with IDH-mutant gliomas in the future. Doctors may also prescribe this medication off-label to other groups of people with IDH-mutant gliomas. Off-label use happens when a doctor prescribes a treatment in a way that the FDA has not specifically approved.

A phase 3 clinical trial found that treatment with vorasidenib after surgery reduced the chances that a grade 2 IDH-mutant glioma would continue to grow or come back, compared with treatment with surgery alone.

Most side effects and adverse reactions to vorasidenib were mild. Less than 4% of people who received vorasidenib in this trial stopped taking the medication due to adverse reactions.

Scientists are also studying other IDH inhibitors for IDH-mutant gliomas, including:

  • BAY1436032
  • ivosidenib (Tibsovo)
  • olutasidenib (Rezlidhia)
  • crelosidenib (LY3410738)
  • ranosidenib (HMPL-306)
  • safusidenib (DS-1001b)

The FDA has already approved ivosidenib and olutasidenib to treat IDH-mutant acute myeloid leukemia, a type of bone marrow and blood cancer.

Ongoing research will help scientists learn whether these medications or other IDH inhibitors work well to treat IDH-mutant gliomas.

Researchers are conducting clinical trials to test other types of targeted therapies for IDH-mutant gliomas.

GLS inhibitors

GLS inhibitors block the action of glutaminase (GLS), an enzyme that helps convert energy to a form that brain cells can use. Blocking GLS may help stop IDH-mutant gliomas from getting the energy they need to survive and spread, especially when a GLS inhibitor is combined with other forms of treatment.

CB-839 (Telaglenastat) is a GLS inhibitor researchers are currently studying in a phase 1 clinical trial. Participants in the trial are given this drug in combination with chemotherapy and radiation therapy to treat IDH-mutant astrocytomas.

PARP inhibitors

PARP inhibitors block the action of poly (ADP ribose) polymerase (PARP), a family of proteins that help repair damaged DNA. Blocking PARP may stop cancer cells from repairing damaged DNA, which may kill the cancer cells or stop them from dividing.

Researchers are conducting clinical trials to learn whether the following PARP inhibitors on their own or combined with other treatments may be effective for treating IDH-mutant gliomas:

  • niraparib (Zejula)
  • olaparib (Lynparza)
  • pamiparib (Partruvix)

The FDA has already approved niraparib and olaparib to treat some other types of cancer, such as certain types of ovarian or breast cancer.

CDK4/6 inhibitors

Recurrent IDH-mutant gliomas that come back after treatment are often missing the CDKN2A/B gene. This gene is a tumor suppressor gene that gives your body instructions for making inhibitors of CDK, which block the action of cyclin-dependent kinases (CDKs). CDKs are proteins that help tumor cells grow.

Scientists have developed multiple inhibitors of CDK to help block the growth and spread of certain types of cancer that have CDK gene changes.

Researchers are conducting clinical trials to learn whether the following CDK4/6 inhibitors may help treat IDH-mutant oligodendrogliomas that have come back after treatment:

  • abemaciclib (Verzenio)
  • palbociclib (Ibrance)

The FDA has already approved these two drugs for treating certain types of breast cancer.

DNMT inhibitors

DNMT inhibitors are also known as demethylating agents. They block the action of DNA methyltransferases (DNMTs), which are enzymes that play a role in DNA methylation. This is a process that adds carbon and hydrogen atoms to DNA to help control gene expression.

Blocking DNMT may change how certain tumor cells follow the instructions provided by their genes. This might change how the tumor cells work in ways that reduce their growth or spread.

Researchers are currently studying the following DNMT inhibitors for treating certain types of IDH-mutant gliomas:

  • decitabine and cedazuridine (ASTX7272)
  • 5-azacytidine (azacitidine)

Multiple studies are underway to test immunotherapies for IDH-mutant gliomas, including the immune checkpoint inhibitors and vaccines describes below.

Immune checkpoint inhibitors

Immune checkpoint inhibitors are medications that block the action of immune checkpoints. These are proteins on the surface of T-cells that play an important role in your immune system. Some tumor cells have proteins that bind to immune checkpoints, which tells the T-cells to turn off, which stops your immune system from fighting the tumor.

Blocking the action of immune checkpoints may help T-cells in your immune system recognize and attack certain types of tumor cells.

Researchers are studying the following immune checkpoint inhibitors to learn whether they work well on their own or combined with other treatments for IDH-mutant gliomas:

  • avelumab (Bavencio)
  • pembrolizumab (Keytruda)
  • nivolumab (Opdivo)

The FDA has already approved these checkpoint inhibitors for treating other types of cancer.

Vaccines

Cancer vaccines train your body to recognize and attack certain types of cancer cells.

Researchers are currently developing and testing multiple vaccines to help strengthen the immune system response against IDH-mutant glioma cells.

If you develop a glioma, your doctor will likely order tests to learn whether the glioma tumor cells have mutations in the IDH1 gene, IDH2 gene, or other genes. Your treatment options and outlook may partly depend on the specific gene changes that the tumor cells have.

Conventional treatments for IDH-mutant gliomas include surgery, radiation therapy, and chemotherapy. The FDA has also recently approved vorasidenib, a type of targeted therapy for treating grade 2 IDH-mutant gliomas in adults and children ages 12 years or older who have had surgery to remove some or all of the tumor.

Researchers are conducting clinical trials to learn whether other targeted therapies or immunotherapies may help treat newly diagnosed IDH-mutant gliomas or recurrent IDH-mutant gliomas that have returned after treatment.

A clinical trial is a type of study that helps researchers understand how safe and effective a treatment is. Your doctor might encourage you to take part in a clinical trial if they think you might benefit from getting a treatment that scientists are still studying. They can help you understand the potential benefits and risks.

Clinical trials are helping scientists identify the safest and most effective treatments for IDH-mutant gliomas. New and emerging treatments may help improve treatment options and outlooks for people with these tumors.

Talk with your doctor to learn about your treatment options, including the potential benefits and risks of different treatment approaches.