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Misunderstood leukemia
To say that the Chinese people are most familiar with the type of cancer, I am afraid that it is "leukemia". And in the hearts of many people, they all think that leukemia is a terminal disease, and if you get it, you will die.
Why is there such an impression? Mainly because I watch too many TV dramas, especially Japanese dramas and Korean dramas! According to statistics, hundreds of male and female protagonists in hundreds of film and television works in China, Japan and South Korea have died of leukemia! Long-term brainwashing has made everyone firmly believe that leukemia cannot be cured.
In the popular Japanese TV series "Blood Doubt" in the 70s and 80s, the heroine got leukemia, commonly known as "blood cancer". At that time, leukemia was indeed very difficult to treat, and the survival rate was very low. The screenwriter needs the protagonist to have a serious radiation-related disease, and the name "blood cancer" is particularly easy for the people to understand, so they use it.
But more than 30 years later, the situation has long changed, and the concepts of screenwriters and ordinary people must be updated. In fact, leukemia as a whole is already one of the cancer types with the highest survival rates.
Some of these subtypes, such as acute leukemia in children (ALL) and chronic myelogenous leukemia (also called chronic myeloid leukemia, abbreviated CML) in adults, now have a five-year survival rate of more than 90%! Leukemia is not a terminal illness for a long time!
Interestingly, the two leukemias have high survival rates for very different reasons: pediatric acute lymphoblastic leukemia relies mainly on advances in chemotherapy and stem cell transplantation; while chronic myelogenous leukemia relies on the continuous introduction of new generations of targeted drugs.
Chronic myelogenous leukemia can be divided into chronic, accelerated, and blast phases. Once you enter the period of rapid change, the condition deteriorates rapidly, and treatment will be very difficult. Therefore, prolonging the residence time of the disease in the chronic and accelerated phases as much as possible is very important to control disease progression and improve patient survival.
More than 90% of chronic myelogenous leukemia is caused by mutations in the BCR-ABL fusion gene, and the occurrence of this mutation will cause some blood cells to deteriorate and grow out of control. In response to this mutation, scientists spent decades to finally develop the targeted drug imatinib. It can effectively inhibit the activity of mutant genes, and is the first targeted new drug in history to be developed for tumor mutant genes in the true sense.
In the famous movie "I Am Not a Medicine God", the medicine they went to India to buy was imatinib.
The image comes from the internet
In 2001, the emergence of imatinib jumped from 30% to 90% of the 5-year survival rate of chronic myeloid leukemia, completely changing the fate of this group of patients. Today, 20 years later, most of the first patients to take this drug are still alive, and many are working normally, getting married and having children.
What was once fatal, leukemia, became a chronic disease.
Second- and third-generation drugs appear
Science doesn't stop there, because there are still patients who need help.
Like other targeted drugs, imatinib can also face the problem of drug resistance. Although most patients with chronic myelogenous leukemia can survive for a long time after using imatinib, many people are not so lucky, the main reason is the progression of the disease caused by drug resistance.
Studies have found that many of the drug resistance is due to new mutations in the BCR-ABL gene of tumor cells, resulting in imatinib can no longer work, and common types include T315I mutations, E255K mutations and so on.
What to do? Develop a new generation of targeted drugs!
A few years after the emergence of imatinib, second-generation targeted drugs began to gradually appear, such as nilotinib, dasatinib, bosutinib and so on. With the second-generation drug on the market, a subset of patients who use imatinib-resistant drugs can reap the benefits and even survive for a long time.
But second-generation drugs can't solve all the problems, and the most headache is the mutation T315I. The study found that cancer cells carrying this mutation are resistant to all first- and second-generation drugs.
And what to do? Continue to develop three generations of targeted drugs! The main goal is to overcome the difficult T315I mutation.
Although three generations of targeted drugs were already listed overseas a few years ago, China did not. Therefore, for a long time, Chinese patients with T315I mutations have been facing a situation where there is no cure. Until November this year, the domestic original research of the third generation of targeted drug orebatinib was approved for marketing in China, only to fill this gap.
Orebatinib is a new anti-cancer drug "Born in China, made in China". Its earliest compound came from the domestic research and development team, and was later developed by China's Yasheng Pharmaceutical. I saw a recent interview, the development of orebatinib from the establishment of the project in 2008, the start of preclinical trials in 2013, 2016 into clinical trials, and then to the market in 2021, a full 13 years. The difficulty of developing new anti-cancer drugs can be seen.
At the recently concluded 2021 American Society of Hematology Annual Meeting, the latest data for orebatinib were released.
One of the most important indicators of anticancer drugs is to look at survival, and when orepatinib is used in patients in the chronic phase, the 24-month progression-free survival rate is 91.9% and the overall survival rate is 95%. When used in more dangerous accelerated patients, the 24-month progression-free survival rate was 61.8% and the overall survival rate was 69.1%.
For chronic myelogenous leukemia drugs, there are several special indicators that are very important, such as the complete hematologic response rate (CHR), the complete cytogenetic response rate (CCyR), etc., the specific explanation is more complicated, but we only need to know that these indicators are describing the effect of a drug to kill and control leukemia cells, the higher the number, the better the effect.
When orebatinib was used in patients in the chronic phase, the median duration of treatment was 25.8 months, and the complete hematologic response rate (CHR) was 100% in the assessable patients and the major cytogenetic response rate (MCyR) was 81%, and in the accelerated phase, the median duration of treatment was 19.7 months, and the primary hematologic response rate (MaHR) was 74%.
Simply put, whether in the face of patients in the chronic or accelerated stages, orebatinib has shown good results. Compared with similar drugs abroad, safety seems to have some advantages. With the approval of this drug, Chinese patients have taken another step towards the goal of turning chronic myeloid leukemia into a chronic disease.
Everyone will definitely ask, now that there are so many first-generation/ second-generation / third-generation targeted drugs, how should patients with slow myeloid leukemia choose? Is it one generation that uses the second generation, and the second generation uses the third generation?
At present, the first-line drugs for Chinese patients can consider first- or second-generation targeted drugs, and many patients can benefit from long-term benefits. However, if the first-line treatment effect is not good, there is a warning or drug resistance, genetic testing is recommended, and based on the test results, it is accurate to assess how to change the dressing. If it is indeed a T315I mutation, then the third generation of drugs should be considered directly.
In addition, bone marrow transplantation or chemotherapy may also be considered.
Future outlook
Cancer treatment has changed dramatically over the past few decades.
It is hard to imagine that 40 years ago, leukemia was basically terminal, and few patients could live past 5 years. 20 years ago, patients with chronic myelogenous leukemia mainly relied on interferon and chemotherapy, which had poor treatment effects and strong side effects.
Up to now, patients with chronic myelogenous leukemia have nearly 10 new targeted drugs, from the first generation, the second generation to the third generation. Cancer cells continue to mutate in an attempt to escape the inhibition of anti-cancer drugs, and scientists are also developing new targeted drugs and playing "cat and mouse" games with cancer cells.
With the emergence of these targeted drugs, as long as the drug is taken on time, standardized follow-up, regular monitoring, and timely detection, the life expectancy of many patients with chronic myelogenous leukemia can be no different from that of normal people!
As long as everyone can be full of confidence, study seriously, use drugs correctly under the guidance of precision medicine and standardized diagnosis and treatment, and do not delay treatment, more and more cancers will become chronic diseases.
Hail to life!
*This article aims to popularize the science behind new cancer drugs, not drug promotional materials, let alone treatment plan recommendations. For guidance on treatment options, visit a regular hospital.
bibliography:
1. Chronic myeloid leukaemia. Lancet. 2015 Apr11;385(9976):1447-59.
2. Inhibitors of ABL and the ABL-T315Imutation. Curr Top Med Chem. 2008;8( 10):905-21.
3. Novel BCR-ABL1 tyrosine kinase inhibitorsin the treatment of chronic myeloid leukemia. Expert Rev Hematol. 2021 Oct20;1-4.
4. Updated Safety and Efficacy Results ofPhase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABLTyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic MyeloidLeukemia (CML). ASH abstract #311, 2021
5.Updated Results of Pivotal Phase 2 Trialsof Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor(TKI)-Resistant BCR-ABL1T315I-Mutated Chronic- and Accelerated-Phase ChronicMyeloid Leukemia (CML-CP and CML-AP). ASH abstract #3598, 2021
6. Hematology Branch of Chinese Medical Association. Chinese Guidelines for the Diagnosis and Treatment of Chronic Myeloid Leukemia (2020 Edition), Chinese Journal of Hematology,2020,41(05): 353-364.
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