Will "V" save "Emergency"!

If there is a vote for everyone to choose which cancer is the most feared, then the number of votes for leukemia will definitely not be small
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Compared with the giant monsters of solid tumors such as lung cancer and liver cancer, the incidence of leukemia is not high, but it is dangerous and the suffering of patients, I believe everyone has heard of it
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Fortunately, with the continuous progress of medicine, the treatment of leukemia has gradually entered the era of precision treatment.
Clinically, patients can be stratified according to cytogenetic/molecular biology analysis, and the most appropriate individualized treatment strategy can be selected.
patient survival prognosis
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For some therapeutic targets with outstanding value, precision targeted therapy drugs have also begun to enter the market in an all-round way
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Remember the IDH1 mutation that has repeatedly appeared in top journals and is expected to be the key to the breakthrough of precision treatment of many rare cancers? It is one of the most interesting therapeutic targets in AML
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With the approval of the IDH1 inhibitor ivonib in China for the treatment of patients with relapsed/refractory (R/R AML) IDH1-mutated AML, China's AML patients have finally ushered in a precision treatment option
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But only by fully understanding the disease can we understand why precision therapy is so desperately desired by AML patients
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Fighting malignant cancers of the blood system is also very important.
The "killer" AML for the elderly is the type of leukemia with the highest incidence among adults.
According to the 2017 Global Burden of Disease Study (GBD) data, there are about 120,000 new AML cases in the world every year.
For example, accounting for 23.
1% of all leukemias, and about 100,000 people died of AML, accounting for 28.
7% of all leukemia deaths [1]
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However, if the incidence rate is calculated according to the population, AML is still a rare cancer (the incidence rate is less than 6 cases per 100,000 people).
The data shows that there are about 13,200 new cases of AML in China each year, and about 7,100 people die from AML.

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However, another major epidemiological feature of AML is that patients are mainly concentrated in the elderly population.
The median age at diagnosis is about 65-70 years old.
The incidence rate of people aged ≥65 years is 10 times that of people aged <65 years [2].
It is very different from other types of leukemia
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The intensification of the aging trend of China's population means that there will be more AML patients in the future
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This characteristic also has a significant impact on the treatment of AML.
At the peak of the diagnosis of AML, the elderly will almost certainly suffer from chronic diseases such as hypertension and diabetes.
Affecting tolerance to treatment, various treatment-related adverse reactions and complications should not be underestimated
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Treating elderly cancer patients is never an easy task, and don’t forget, the full name of AML has the word “acute”.
It will quickly inhibit normal hematopoiesis and infiltrate the body everywhere, from symptoms to life-threatening patients, ranging from a few months to a few days, it is quite dangerous
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The patient's advanced age, dangerous disease, and traditional treatment methods are not conducive to the prognosis of AML patients
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Even in the United States with a high level of medical care, AML has been a type of leukemia with the worst prognosis for many years.
The 5-year survival rate of patients only exceeded 20% from 2008 to 2013, and the 5-year survival rate of patients over 60 years old is still less than 15% [ 3]
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The 5-year survival rate of AML patients aged <60 and ≥60 years admitted to MD Anderson Cancer Center (Image source: Blood Cancer Journal) That is to say, AML has the characteristics of the highest incidence, relatively acute onset, and very poor prognosis.
It is not difficult to understand the urgent expectations of patients for new therapeutic drugs
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Fortunately, the treatment of AML has progressed well in recent years, and now more IDH1 inhibitors are developing in parallel with a variety of treatment strategies
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What weapons do we have in the fight against AML? Because the age of diagnosis of AML patients is generally too old, various guidelines or consensuses often use the age of 60 as the dividing line.
For patients on both sides of this age line, different anti-leukemia treatment strategies are recommended
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In contrast, the traditional treatment drugs for AML are somewhat "unchangeable"
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For example, for the initial induction of remission therapy for patients < 60 years old, classical chemotherapy drugs such as cytarabine (Ara-C), daunorubicin (DNR) and homoharringtonine (HHT) discovered by Chinese scholars are still the main Optionally, patients who successfully achieve remission after induction therapy can continue chemotherapy or receive hematopoietic stem cell transplantation
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For patients ≥60 years old who can tolerate intensive induction therapy, Ara-C single-agent medium-high-dose or combination therapy is widely used, while patients who cannot tolerate it often use low-dose Ara-C, or diazepam Two demethylating drugs, citabine and azacitidine, were used, and the follow-up treatment plan was determined according to the remission
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In terms of precision targeted therapy, IDH1/2 mutations and FLT3 mutations are currently mentioned in the guidelines.
For patients with FLT3 mutations, targeted inhibitors such as Gilteritinib and Midostaurin are used in first-line and later-line therapy.
have already been applied
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For patients with IDH1/2 mutation detected, domestic and foreign guidelines still recommend that special targeted drugs such as ivonib (IDH1) should be preferred, especially for R/R AML patients with difficult treatment and poor prognosis, 2021 The Chinese Medical Association guidelines recommended the combination of IDH1 inhibitors with demethylating drugs or BCL-2 inhibitors [4]
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The latest recommendation of the 2022 NCCN guidelines for patients aged ≥ 60 years who cannot tolerate intensive induction therapy.
In February 2022, ivonib was officially approved in China for the treatment of R/R AML with IDH1 mutations.
Chinese patients finally It can also be officially recommended by the guidelines and use more powerful treatment plans, which also means that the clinical detection of IDH1 mutations needs to keep pace with the times.

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To test or not to test, let the treatment have the final say.
In order to give more patients the opportunity for precise targeted therapy, it is imperative to improve the detection of IDH1/2 mutations
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Although in the era of chemotherapy, a number of studies analyzing IDH1/2 mutation and the prognosis of AML patients have not clearly indicated a clear association between the two [6-7], the situation may be different after the emergence of precision targeted therapy drugs
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For example, at the 2020 American Society of Hematology (ASH) annual meeting, an analysis of a total of 276 IDH1/2-mutant AML patients showed that the proportion of patients with IDH mutations increased with age, but IDH1/2 mutations were not considered as a independent predictor of prognosis [6]
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Some data show that patient age and co-mutations such as NPM1 and DNMT3A may affect the tumor biological behavior of AML and the effect of chemotherapy, but considering the important impact of IDH mutation on the occurrence and development of cancer, such patients may be one of the AML patients.
Class-independent molecular typing should give priority to targeted therapy as much as possible
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Evaluation of the impact of IDH1/2 mutation on the prognosis of AML patients (Image source: Blood) "Precision treatment, testing first", the 2021 US NCCN guidelines have listed IDH mutation as a must-check item for comprehensive molecular diagnosis of AML, and recommends that it be checked in each course of the disease.
In each stage, multi-gene Panel or next-generation sequencing (NGS) with more information is used for detection, so as to better guide the whole-process management of the disease
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In contrast, due to the availability of testing and drugs, the recommendations for testing in China’s AML diagnosis and treatment guidelines are different.
For example, in the Chinese Society of Clinical Oncology (CSCO) guidelines for the diagnosis and treatment of hematological malignancies, class I recommends newly diagnosed patients aged ≥ 60 years.
Detection of IDH1/2 mutations, but only category II recommendations for detection of newly diagnosed patients <60 years of age, and weaker recommendations for NGS testing (category III)
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However, for R/R AML patients with poor prognosis, both the CSCO guidelines and the Chinese Medical Association guidelines recommend improving the detection of molecular expression profiles including IDH1/2 mutations, so as to provide patients with possible targeted therapy opportunities.
Such targeted drugs also indeed reflect the effect of improving survival and quality of life
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Treatment drives testing, testing supports treatment, and the complementarity between the two will ultimately translate into patient benefits
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As the world's first small-molecule inhibitor targeting IDH1 mutations, the clinical research of ivonib is still advancing.
The pivotal clinical study AGILE has been successful, and the indication application has been granted priority review status by the US FDA
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Next time, Singularity Cake should talk about a series of outstanding achievements of Avonib in clinical research
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References: 1.
Yi M, Li A, Zhou L, et al.
The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: estimates based on the global burden of disease study 2017[ J].
Journal of Hematology & Oncology, 2020, 13(1): 1-16.
2.
Shallis RM, Wang R, Davidoff A, et al.
Epidemiology of acute myeloid leukemia: recent progress and enduring challenges[J].
Blood Reviews, 2019, 36: 70-87.
3.
Kantarjian H, Kadia T, DiNardo C, et al.
Acute myeloid leukemia: Current progress and future directions[J].
Blood Cancer Journal, 2021, 11(2): 1-25.
4.
Chinese Medicine Chinese Society of Hematology, Leukemia and Lymphoma Group.
Guidelines for the diagnosis and treatment of adult acute myeloid leukemia (non-acute promyelocytic leukemia) in China (2021 edition) [J].
Chinese Journal of Hematology, 2021, 42(8): 617-623 5.
Zarnegar-Lumley S, Alonzo TA, Othus M, et al.
Characteristics and prognostic effects of IDH mutations across the age spectrum in AML: a collaborative analysis from COG,SWOG, and ECOG[J].
Blood, 2020, 136(S1): 31-32.
6.
Duchmann M, Micol JB, Duployez N, et al.
Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study[J].
Blood, The Journal of the American Society of Hematology, 2021, 137(20): 2827-2837.
The author of this articleTan Shuo