​Some drug-resistant leukemias have new treatment options!

▎The content team editor of WuXi AppTec recently, a drug for the treatment of some leukemia patients-Olverembatinib (Code: HQP1351) was approved for marketing by the National Medical Products Administration (NMPA) of China.
The indications are: It is used for the treatment of any tyrosine kinase inhibitor (TKI) resistance, and is diagnosed as chronic myelogenous leukemia (CML) with T315I mutation in adult patients in the chronic or accelerated phase using fully validated detection methods
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Screenshot source: NMPA official website According to the information on the NMPA official website, oribatinib is the first drug approved for the indication of chronic myeloid leukemia with T315I mutation in mainland China, providing effective treatment for patients who are resistant to T315I mutation Treatment methods
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Malignant tumors related to white blood cells believe that many people have read "I am not the god of medicine", and the medicine mentioned in it is one of the medicines for the treatment of chronic myelogenous leukemia
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Chronic myelogenous leukemia (CML, often referred to as chronic myelogenous leukemia), is a malignant tumor related to white blood cells, accounting for about 15% of adult leukemia
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The global annual incidence rate is about (1.
6-2) per 100,000 people, and the annual incidence rate in China is (0.
36-0.
55) per 100,000 people
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With the increase of age, the incidence of CML tends to increase gradually
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The natural course of CML includes chronic phase, accelerated phase and blast phase
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90%-95% of patients are in the chronic phase when they are first diagnosed; the accelerated phase and the blast phase belong to the advanced stage of the disease.
The clinical manifestations of this period are a gradual and gradual process that is difficult to separate absolutely, and about 20%- 25% of patients did not go through the accelerated phase, they directly entered the blast phase
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The main clinical manifestations of patients in the chronic phase are anemia and splenomegaly related symptoms, including fatigue, weight loss, malaise, anorexia, early satiety, pain and discomfort in the left upper abdomen or abdomen
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There are generally no bleeding symptoms in the early stage, and about 30% of patients have bleeding of varying degrees in the later stage, such as epistaxis, gum bleeding, skin ecchymosis, gastrointestinal bleeding, and retinal bleeding
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Women may have menorrhagia
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Patients in the advanced stage have increased wasting symptoms, such as unexplained fever, fatigue, anorexia, night sweats, and increased weight loss; some patients also experience headaches, bone and joint pain, rapid spleen enlargement disproportionately with leukocytosis and accompanied by tenderness , suddenly swollen lymph nodes, anemia, progressive increase and so on
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In addition, in addition to the above-mentioned advanced symptoms, patients in blast stage may also have extramedullary infiltration, such as skin nodules, testicular infiltration, priapism, and orbital infiltration and green tumors
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Patients in the blast stage may also experience severe infections and bleeding symptoms, which are life-threatening
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Image source: 123RF patients urgently need more effective treatments and new drugs.
CML treatment has undergone a series of treatment measures such as radiotherapy, chemotherapy, immunotherapy, bone marrow transplantation, and molecular targeted therapy, and the efficacy has gradually improved
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Especially in the late 1990s, the first-generation tyrosine kinase inhibitor Imatinib mesylate (IM) was successfully used in clinical practice, becoming a milestone in the treatment of CML and allowing CML treatment to enter the molecule In the era of targeted therapy, patients can achieve long-term survival
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Unfortunately, although the first-generation tyrosine kinase inhibitors and several subsequent second-generation drugs have significant clinical benefits for the treatment of CML, acquired resistance has always been the main challenge for the treatment of CML
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For example, mutations in the kinase region of BCR-ABL are one of the important mechanisms leading to acquired drug resistance.
Among them, T315I mutation is one of the common types of drug-resistant mutations, and the incidence rate in drug-resistant CML is as high as about 25%
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For patients with drug resistance, effective new drugs are urgently needed
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Image source: 123RF third-generation BCR-ABL inhibitor oribatinib is a small molecule protein tyrosine kinase inhibitor, belonging to the third-generation BCR-ABL inhibitor, which can effectively inhibit BCR-ABL tyrosine kinase The activity of wild-type and multiple mutants can inhibit the phosphorylation of BCR-ABL tyrosine kinase and downstream proteins STAT5 and Crkl, block downstream pathway activation, and induce BCR-ABL positive and BCR-ABL T315I mutant cell lines.
Cell cycle arrest and apoptosis can be used to treat CML patients who are resistant to first- and second-generation tyrosine kinase inhibitors
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In December 2020, the results of two phase 2 studies released at the 62nd American Society of Hematology (ASH) annual meeting showed that oribatinib is effective in CML with T315I mutation and resistance to tyrosine kinase inhibitors.
Both the chronic phase and the accelerated phase showed good efficacy and tolerability, and as the treatment time was extended, the remission rate and depth of remission further increased
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These two studies, named HQP1351-CC201 and HQP1351-CC202, were respectively aimed at patients in the chronic and accelerated phases of tyrosine kinase inhibitor-resistant CML with T315I mutations
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Specifically, the HQP1351-CC201 study: As of March 23, 2020, a total of 41 patients with chronic CML were included, with a median follow-up time of 7.
9 months
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The 3-month progression-free survival (PFS) rate of patients was 100%, the 6-month progression-free survival rate was 96.
7%, and the main cytogenetic response rate was 75.
6%, of which 65.
9% had a complete cytogenetic response, and 48.
8% of patients Achieve major molecular biological relief
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The most common grade 3/4 grade hematology treatment-related adverse reaction was thrombocytopenia, and no treatment-related deaths occurred
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HQP1351-CC202 study: As of February 11, 2020, a total of 23 patients with accelerated CML were included in the study, with a median follow-up time of 8.
2 months
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The 3-month progression-free survival rate of patients was 100%, the 6-month progression-free survival rate was 95.
5%, and the major hematological response rate was 78.
3%, of which the complete hematological response rate was 60.
9%, and the major cytogenetic response rate was 52.
2 %, of which 39.
1% achieved a complete cytogenetic response, and 26.
1% of patients achieved major molecular biological remission
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The most common grade 3/4 grade 4 hematology treatment-related adverse reaction is thrombocytopenia
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Image source: 123RF We expect that with the approval of Orebatinib in China, it will bring new treatment options to specific leukemia patients and benefit more patients
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Chinese Guidelines for Diagnosis and Treatment of Chronic Myeloid Leukemia (2020 Edition).
Chinese Journal of Hematology, DOI: 10.
3760/ cma.
j.
issn.
0253-2727.
2020.
05.
001.
[2] Standards for Diagnosis and Treatment of Chronic Myeloid Leukemia (2018 Edition) [3] The State Food and Drug Administration has conditionally approved the listing of Orebatinib tablets.
Retrieved Nov 25 ,2021, from https:// [4] Ascent Pharmaceuticals Oribatinib (HQP1351) is planned to be included in the breakthrough treatment product, which is the first three-generation BCR-ABL inhibition in China Retrieved Nov 25 ,2021, from https:// [2020ASH] Ascentage Pharmaceuticals announces the criticality of its new anti-drug-resistant leukemia drug HQP1351 (oribatinib) Register positive data for Phase II study.
Retrieved Nov 25 ,2021, from https:// Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
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This article is not a recommended treatment plan
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If you need guidance on treatment plans, please go to a regular hospital for treatment
.