Precision therapy for leukemia!

▎WuXi AppTec content team editor Recently, an IDH1 inhibitor, Avonib tablets (trade name: Tosuwo®), has been approved by the China National Medical Products Administration (NMPA) for marketing, and the indication is "for Treatment of adult patients with relapsed or refractory acute myeloid leukemia (R/R AML) harboring an IDH1 susceptibility mutation"
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Screenshot source: The public information on the NMPA official website shows that the approval of Avnib tablets will provide a new precision treatment option for patients with acute myeloid leukemia
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About leukemia Leukemia is a common hematological malignancy.
According to the differentiation and maturity of leukemia cells, natural history and main involved cell series, it can be divided into acute leukemia (AL) and chronic leukemia (CL): acute leukemia (AL) , the disease develops rapidly, the natural course is only a few months, and can be divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML); chronic leukemia (CL), the disease develops slowly, with a natural course of several years, can be divided into Chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), and rare types of leukemia
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In China, there are more patients with acute leukemia than chronic leukemia (about 5.
5:1), among which acute myeloid leukemia is the largest with an incidence of 1.
62/100,000, followed by acute lymphoblastic leukemia with an incidence of 0.
69/100,000
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In recent years, with the aging of the population, the incidence of acute myeloid leukemia in China has been increasing year by year
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According to data released by the International Agency for Research on Cancer (IARC), there will be 85,000 new leukemia patients in China in 2020, resulting in 62,000 deaths
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About 60% of new leukemia patients are acute myeloid leukemia, and among these patients, about 6%-10% carry IDH1 mutations
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Historically, existing treatments for patients with IDH1-mutated acute myeloid leukemia have been limited, with low 5-year survival rates and poor patient quality of life
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Image source: 123RF on relapsed or refractory acute myeloid leukemia "Chinese Society of Clinical Oncology (CSCO) Malignant Hematology Diagnosis and Treatment Guidelines 2020" points out that any one of the following is relapsed or refractory acute myeloid leukemia: after the standard The first treatment patients who were ineffective after 2 courses of treatment; patients who relapsed within 12 months after consolidation and intensive therapy after complete remission (CR); patients who relapsed after 12 months but were ineffective after conventional chemotherapy; 2 or more times Patients with relapse; patients with persistent extramedullary leukemia
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Image source: 123RF About Ivornib Ivornib is an oral targeted inhibitor of IDH1 mutant enzymes, which was approved for marketing in China based on a Chinese registration bridging study CS3010-101
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This study was designed to evaluate the pharmacokinetics, pharmacodynamics, safety, and clinical efficacy of ivonib orally in Chinese patients with IDH1-susceptible mutations and adult patients with relapsed or refractory acute myeloid leukemia
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Study results show excellent clinical efficacy and good tolerability of ivonib in adult Chinese patients with relapsed or refractory acute myeloid leukemia harboring susceptible IDH1 mutations: in 30 evaluable patients , the primary efficacy endpoint—complete remission and complete remission with partial hematologic recovery (CR+CRh) rate was 36.
7% (11/30, 11 patients achieved complete remission); the median time to CR+CRh was 3.
68 months, the 12-month CR+CRh sustained remission rate was 90.
9%
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Two patients underwent hematopoietic stem cell transplantation (HSCT) after achieving complete remission or complete remission with partial hematologic recovery
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The median event-free survival (EFS) was 5.
52 months, and the median overall survival (OS) was 9.
10 months
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Ivornib was well tolerated and had a manageable safety profile
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The incidence of adverse events (TEAEs) of grade 3 or higher was 86.
7%, and the incidence of TEAEs leading to permanent discontinuation was 10%; no new safety signals were found, and adverse events of special concern could be obtained through protocol guidance and routine clinical management.
Effective monitoring and control
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Image source: 123RF In the U.
S.
, ivonib has been approved for multiple indications, including adult patients with relapsed or refractory AML with IDH1 mutations, those with IDH1 who are ≥75 years of age or who cannot receive intensive chemotherapy because of other comorbidities Adult patients with newly diagnosed AML with a susceptibility mutation and adults with locally advanced or metastatic cholangiocarcinoma harboring IDH1 mutations
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We expect that with the approval of ivonib in China, it will bring new treatment options and hope to more acute myeloid leukemia patients, helping them improve their quality of life and prolong their lives
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Recommended reading This disease with a fatality rate close to 100%, but 100% preventable, has a new prevention option for the treatment of thalassemia! Significantly reduces the burden of blood transfusion, a common life-threatening virus, new anti-infection drugs improve the survival of lymphoma patients, broad-spectrum anti-tumor drugs are approved for the treatment of this blood system disease, and TPO receptor agonists are approved for marketing reference Information [1] Information release of drug approval documents pending collection on February 9, 2022.
Retrieved Feb 10, 2022, from https:// 2] First of its kind: CStone’s registration study of evonib in patients with relapsed or refractory acute myeloid leukemia in China has met expectations, and the NDA has been accepted by the China National Medical Products Administration.
Retrieved Feb 10, 2022, from https://mp.
weixin.
qq.
com/s/2sEA-UDS19aiX7C-TNJBVQ[3] ESMO 2021| CStone Announces Avonib in Relapsed/Refractory Acute Myeloid Leukemia Patients with Susceptible IDH1 Mutation The Chinese registration bridge study clinical data.
Retrieved Feb 10, 2022, from https://mp.
weixin.
qq.
com/s/vUf1x52OmyqY-yGWZrK20A[4] CStone Pharmaceuticals announced the first domestic IDH1 inhibitor Tosuvo® ( Avonib Tablet) was approved in China, providing a new treatment option for patients with acute myeloid leukemia.
Retrieved Feb 10, 2022, from https://mp.
weixin.
qq.
com/s/Cx_0jgrvAOIYBCqqobXwJQ[5] Junbo Ge, Yongjian Xu , Chen Wang.
Internal Medicine [M].
9th Edition.
Beijing: People's Health Publishing House, 2018.
Disclaimer: WuXi AppTec content team focuses on introducing global biomedical health research progress
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This article is for information exchange purposes only, and the views expressed in this article do not represent WuXi AppTec's position, nor do they represent WuXi AppTec's support or opposition to the views expressed in this article
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This article is also not a treatment plan recommendation
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For guidance on treatment options, please visit a regular hospital
.