Glioma is a common intracranial malignant tumor, accounting for about 60% of all intracranial tumors, with the characteristics of "three highs and one low" of incidence, recurrence, mortality and low cure rate.
According to statistics, 16 people per 100,000 people are affected. Because gliomas grow aggressively and have no obvious demarcation with brain tissue, it is difficult to achieve total resection, and can not be effectively cured by traditional surgery alone. However, the existing tumor drugs and radiotherapy mostly target the growing cells, but they cannot do anything against the cancer stem cells in a quiescent state.
According to the criterion of "presence or absence of IDH mutation and 1p/19q combined deletion", diffuse gliomas are classified into 5 subtypes, including:
IDH野生型胶质母细胞瘤;
IDH-mutant glioblastoma;
IDH 野生型星形胶质细胞瘤;
IDH-mutant astrocytoma;
Oligodendroglioma with IDH mutation and 1p/19q combined deletion.
In glioma, IDH is included in the NCCN guidelines and the Chinese guidelines for glioma, and the guidelines clearly point out that IDH1/2 is an important molecular indicator for the molecular classification of glioma.
Mutations in the IDH1 and IDH2 genes occur with high frequency in oligodendrogliomas and astrocytomas, as well as in secondary glioblastomas, but are almost absent in primary glioblasts.
The specific mutations are as follows:
Gliomas can occur in people of any age, but they occur more often in adults. Men have a slightly higher chance of developing gliomas than women. With the combination of surgical resection, concurrent chemoradiotherapy and adjuvant chemotherapy, more than 90% of glioma patients still have recurrence and progression.
The progression-free survival and overall survival of different grades of gliomas varied greatly, and the prognosis of low-grade gliomas was relatively better
Glioma IDH1 mutation with ivosidenib
IDH1 mutations are common in glioma, occurring in up to 70% of lower-grade gliomas, with the most common mutation site being R132H. IDH1 mutation is an important pathogenic gene for gliomatogenesis and leads to tumorigenesis by greatly increasing 2-HG levels.
The IDH1 inhibitor ivosidenib precisely targets the IDH1 mutation, effectively inhibits the production of tumor metabolite 2-HG, and restores the normal physiological function of a-KG.
Ivosidenib for the treatment of IDH1-mutant glioma has a good blood-brain barrier pass rate, and the drug concentration of ivosidenib in tumor tissue is 299ng/g.
At the same time, ivosidenib in the treatment of IDH1-mutant glioma can greatly reduce the level of tumor metabolite 2-HG, with an average reduction of up to 92%.
Application and exploration of ivosidenib in IDH1 mutant glioma
- In 2015, ivosidenib was "budding" in an exploratory study of IDH1-mutated advanced glioma
- In 2020, the phase I study of ivosidenib in the treatment of IDH1-mutant glioma topped JCO, with an impact factor of 50.7.
Findings:
1. The median duration of continuous treatment in patients with non-enhancing was 18.4 months, and the longest was 47.2 months, and it was still ongoing.
2. The median PFS of non-enhancing patients was as high as 13.6 months; Among them, the standard therapeutic dose of 500 mg lasted for 15.1 months, which was more than twice that of temozolomide (about 7 months).
3.非增强型(Non-enhancing)患者SD率高达85.7%
4. Ivosidenib is used in patients with IDH1 mutant advanced glioma, which can effectively reduce the tumor growth rate, and the tumor growth rate is reduced from 26% to 9% in 6 months
5. Ivosidenib in the treatment of IDH1-mutant advanced glioma has a good safety profile, with only 19.7% of ≥ grade 3 adverse events, of which only 3% are treatment-related adverse events, and there is no bone marrow suppression
- 2022 National Academy of Sciences: Johns District Hopkins Hospital explores and reports positive findings of ivosidenib in lower-grade glioma with IDH1 mutation
Brief instruction manual for ivosidep
Chinese name of the drug: ivosideb
Drug Chinese trade name: Tuoshuvo ®
Ivosidenib
The English trade name of the drug: TIBSOVO®
Drug alias: Everitinib
Approval time for listing in China: Approved for listing in China in February 2022
Indications for medical insurance: cannot be reimbursed by medical insurance
研发生产厂家：Agios/Patheon Inc./基石药业
Approved indications in the United States:
Tosuvo ® is approved for the treatment of adult patients with relapsed or refractory AML harboring IDH1 mutations;
Adult patients with AML newly diagnosed with IDH1 mutations (aged ≥ 75 years or patients with comorbidities who are unable to receive intensive induction chemotherapy);
Adult patients with relapsed or refractory MDS harboring IDH1 mutations;
For previously treated patients with cholangiocarcinoma harboring IDH1 mutations.
Approved Indications in China:
Tosuvo ® is approved for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring susceptible IDH1 mutations.
Generic drug price: There are generic drugs of ivosidenib in Everest, Bangladesh, and the price is 6000-9000 yuan/box
The Chinese version of Ivosideb
Tips: The medical content involved in this article is a general application suggestion, which is for learning and reference only, and the final opinion is subject to the diagnosis of the clinician.