“Q&A with Dr. M” is a monthly session offered at our brain tumor support group meetings. Group participants ask the questions, and Dr. Aaron Mammoser, neuro-oncologist at Piedmont Brain Tumor Center in Atlanta, provides the answers. Due to its popularity with “group”, Geri Shaffer, SBTF Patient Advocate, brings the Q&A regarding “forever chemo” with Dr. M to this edition of Horizons of Hope. Enjoy!
SBTF:
Hi Dr. Mammoser. Recently an oligodendroglioma patient stated she was being put on “forever chemo”, what does this mean?
Dr. M:
Since it was on an oligo forum, my guess is it was in reference to some of the newer IDH inhibitors.
SBTF:
So IDH inhibitors have been around for a while but there are some new IDH inhibitors?
Dr. M:
There are currently 2 IDH inhibitors approved for use in leukemias and other blood disorders that harbor an IDH mutation, ivosidenib (Tibosovo), which inhibits cells with an IDH-1 mutation, and enasidenib (Idhifa), which inhibits cells with an IDH-2 mutation. Currently, the IDH inhibitor vorasidenib, which inhibits cells with either an IDH-2 mutation or an IDH-2 mutation, is seeking FDA approval for use in treatment of people with IDH mutated low grade glioma.
SBTF:
What are the names of some of the IDH inhibitors being used for Low Grade Gliomas (LGG’s)?
Dr. M:
The majority of brain tumors that are IDH mutated have an IDH-1 mutation. There are several smaller studies demonstrating effectiveness in treating glioma, therefore ivosidenib has been used off label to treat people with an IDH-1 mutated tumor. There is less information about the effectiveness of enasidenib in this setting for people with an IDH-2 mutated tumor, though I’m sure it’s similarly used off label.
Presumably, assuming the FDA approval of vorasidenib is granted, it will become the predominant drug for treating people with IDH mutated low-grade tumors given it can inhibit both of the mutations found in brain tumors and it will have the most scientific data supporting its use.
SBTF:
What does an IDH inhibitor do?
Dr. M:
An IDH inhibitor is a medication which targets a specific mutation in tumor cells, an isocitrate dehydrogenase (IDH) mutation. This is a mutation in the energy pathway in certain tumor cells. These medicines can prevent a tumor from continuing to grow, and in many cases can shrink the tumor. People take the medication daily, indefinitely, similar to the way they would take other medications for high blood pressure, diabetes, or other chronic medical conditions. Essentially, there is no plan to stop the medication unless the person doesn’t tolerate it or unless the tumor becomes resistant to the treatment.
SBTF:
So an IDH inhibitor is NOT a type of chemotherapy?
Dr. M:
Technically, if that’s what is being referred to [by the oligo patient], it’s not a “chemo”, but the term chemotherapy is pretty muddled at this point. Traditionally, “chemo” was a toxic drug that indiscriminately killed cells, tumor and normal cells alike, that were rapidly growing and dividing. We refer to it as “cytotoxic chemotherapy”. Nowadays, the term “chemo” is often “unofficially” used for any drug used to fight cancer. This could entail cytotoxic chemotherapy, immunotherapy, small molecular inhibitors/tyrosine kinase inhibitors, monoclonal antibodies, etc.
SBTF:
Are IDH mutations found in all brain tumors?
Dr. M:
IDH mutations are only found in a small percentage of brain tumors. Studies suggest only about 10-15% of all brain tumors harbor this mutation. However, this mutation is found in the vast majority of “true” low-grade gliomas, or tumors whose cells appear low-grade under a microscope and have no mutations to suggest that it would be expected to behave in a more aggressive fashion.
SBTF:
We recently read in ABTA’s Mind Matters that The IDH1 and IDH2 mutations are found in 80 percent of LGG’s (low-grade gliomas). How does someone know if their tumor contains an IDH1 or IDH2 mutation
Dr. M:
Your oncologist should be able to tell you whether or not your tumor has an IDH mutation.
In general, after surgery, when tumor tissue is sent to the pathology department they will run tests to determine whether or not a tumor harbors an IDH mutation. The initial test is commonly a type of test called an immunohistochemical (IHC) test. This test will pick up about 90% of the cases of an IDH mutation. If the test is negative and there is a high likelihood that the person’s tumor harbors one of the other mutations that make up the remaining 10% (young age, characteristics of tumor that make the presence of an IDH mutation more likely), additional testing is often performed by a method called PCR (polymerase chain reaction).
As of 2021, the World Health Organization changed its brain tumor classification system in such a way that definitive classification of the most common types of glioma is based on the presence or absence of an IDH mutation, therefore all gliomas should have at least IHC testing performed in order to definitively “name” the tumor.
