"A shot of 1.2 million yuan can make cancer cells disappear."
Not long ago, many people were swept away by this news.
This therapy in the news is a car-T treatment.
On June 22, 2021, China approved the marketing of the first CAR-T cell therapy drug (a method of tumor immunotherapy). Recently, the official pricing of the injection was released, as previously speculated - 1.2 million yuan a shot.
At this price, it is not too much to say that it is a "sky-high drug".
This makes many people think: if you are unlucky enough to have cancer, CAR-T therapy needs 1.2 million, is it worth it?
If it were you, how would you choose?
This is not a simple question.
Life is priceless, but after the unfortunate illness, it costs money to cure the disease.
Different people have different answers to this question.
But before answering, it's crucial to clarify these questions.
What exactly can CAR-T treatment do? Which tumor patients are effective? What are the side effects?
Now that cancer treatment has entered the era of precision medicine, CAR-T treatment is by far one of the most effective methods.
CAR-T therapy is an immunotherapy. The so-called immunotherapy is to increase the lethality of immune cells in the body, and immune cells are equipped with directional missiles, directly target tumor cells, and accurately kill [1].
We know that tumor cells are a kind of "traitor" to human cells. It is a series of genetic mutations in normal cells of the human body that become uncontrolled, infinitely growing mutated cells. However, this is not the most powerful superpower of tumor cells.
Evading the "surveillance" of the immune system is one of the most powerful abilities of tumor cells. The human body produces such cells all the time, and the vast majority of them are hunted down by the immune system. Cancer cells can disguise and suppress the function of immune cells, so that they can escape the pursuit of the immune system, and grow and multiply under the eyes of the immune system.
Immunotherapy is specifically aimed at this superpower.
The process is as follows:
1. The hospital collects blood, separates the immune T cells from the blood, and the remaining blood is re-transfused back into the patient's body;
2. Send the isolated T cells to the laboratory or factory;
3. Modification and transformation: through genetic engineering, T cells are equipped with a "aimer" that specifically recognizes molecules on the surface of tumor cells, and the modified T somatic cells are called CAR-T cells, which have super functions of recognizing and killing tumors;
4. Expansion: CAR-T cells modified by modification need to be cultured in vitro to a certain number to meet the treatment requirements, therefore, CAR-T cells need to be cultured in vitro for a large number of expansion;
5. Infusion: CAR-T cells are injected into the patient's body, and CAR-T cells directly recognize the antigens on the surface of tumor cells, thereby killing tumor cells.
The treatment process is simple and short, with blood drawn from the arm, modified, and re-delivered back into the body.
This is shorter than the cycle of chemotherapy and radiation therapy, the patient is less injured, and CAR-T treatment usually requires only 1 to 2 intravenous infusions without repeated administration.
This artificially modified immune cell is a kind of "special force" to fight cancer, capable of killing specific tumor cells.
It can also self-replicate and expand in the human body, continuously replenish "casualty reduction", and stay in patients for a long time and be monitored for immunity.
This therapy is more precise, compared to the side effects of traditional chemotherapy drugs, CAR-T cells can avoid accidental killing of normal cells, less side effects.
Although the effect of immune cell therapy is good, the publicity in the news is exaggerated.
To sum up, immune cell therapy is effective, but the indications are limited and not suitable for all cancers.
CAR-T cell therapy has only made breakthroughs in some hematological tumors, and further research and optimization are needed in the field of solid tumors, which account for a larger proportion of patients [2].
According to the 2020 International Agency for Research on Cancer, the top 10 cancers in China are solid tumors: lung cancer, breast cancer, stomach cancer, colorectal cancer, liver cancer, esophageal cancer, cervical cancer, thyroid cancer, uterine cancer, prostate cancer [3], that is to say, most Chinese cancer patients, currently do not need this new treatment.
However, for hematological tumors, taking leukemia and lymphoma as examples, the traditional first-line treatment methods are chemotherapy, radiotherapy, targeted therapy, etc.
Chemotherapy has many drawbacks. Patients will have many adverse reactions (such as vomiting, hair loss, etc.) and are very painful.
In the field of treatment of refractory and recurrent hematological tumors, the recurrence rate of traditional first-line therapies is high.
According to data released by the World Health Organization's International Agency for Research on Cancer, there will be about 1.28 million new cases of hematological tumors and 650,000 deaths worldwide in 2020;
Hematologic tumors have a high rate of recurrence after first-line treatment, such as patients with diffuse large B-cell lymphoma, and about 30% to 40% of patients with first-line treatment will develop drug resistance or recurrence [3].
After the recurrence, it means that the original treatment is ineffective, and it is more difficult to treat again, which ultimately affects the survival rate.
In contrast, CAR-T therapy is adapted to a wide range of people and has the potential to prolong survival in patients.
Several successful cases of CAR-T cell therapy have been reported.
In July 2019, Aunt Chen was diagnosed with diffuse large B-cell lymphoma (DLBCL), which was alleviated after treatment, but the efficacy was not good after recurrence in 2021.
On June 22, 2021, Aunt Chen received Agironse Injection (a catr-T therapy) at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, and after two months of treatment, Aunt Chen was assessed as having "completely relieved symptoms" and was in better and better physical condition, and was allowed to be discharged from the hospital [4].
The approved CAR-T product, according to the results of the clinical trial released in 2017:
1-year follow-up results: the optimal overall response rate was 82%, and the complete response rate was 54%.
2-year follow-up results: The median follow-up was 27.1 months, and 39% of the subjects continued to respond, of which 37% continued to have a complete response.
Results of the four-year follow-up: the median follow-up time was 51.1 months, the four-year overall survival rate was 44%, and the median survival time (50 percent of patients could survive this time) reached 25.8 months [5].
It should be known that patients who enter this clinical trial are patients with "recurrent or refractory" lymphoma, and conventional radiotherapy and chemotherapy are difficult to achieve such a good effect.
In 2018, there were 3.8 million new cancers in mainland China, and blood tumors accounted for about 9.9%, of which about 20% of patients in acute lymphoblastic leukemia were suitable for sub-second-line therapy, that is, about 70,000 patients, who could benefit from this CAR-T cell therapy.
However, CAR-T cell therapy is not perfect, and it is currently an individualized therapy, the production process is immature and costly; and some patients still have relapses after treatment.
In addition, CAR-T cell therapy also has side effects. One study showed that almost all patients receiving CD19-targeted CAR-T cell therapy experienced different degrees of toxic side effects, such as cytokine release syndrome, and that patients developed fever, which can lead to systemic inflammatory response, hypotension, hypoxia, and organ failure [6].
As of January 2022, only two CAR-T cell drugs in China have been approved for listing, priced at 1.2 million and 1.29 million yuan respectively.
At present, a total of 7 CAR-T cell drugs have been approved for marketing worldwide, and the approved indications are limited to acute lymphoblastic leukemia, multiple myeloma, Hodgkin lymphoma and other hematological tumors [7], which are spent more than one million in China.
Can be described as "sky-high price".
Why is CAR-T cell therapy so expensive?
Behind the high price of CAR-T is a complex issue, involving medicine, pharmacoeconomics, economics, medical industry development and many other aspects.
First, CAR-T treatment needs to be personalized, is an individualized drug, can not achieve large-scale mass production, each batch of products costly, 2 to 4 weeks of culture preparation cycle.
Second, the entire treatment process is very complex, involving many technical links, strict quality control requirements, the global scope has not yet formed a mature, standardized production process, many links rely on manual operation, the failure rate is high.
Third, in terms of industry, the industry is in the early stage of development, and the upstream and downstream resource systems of the industrial chain such as raw materials and equipment are not yet mature, which has also led to higher costs.
From the perspective of drug research and development, in the process of developing this drug, pharmaceutical companies have paid high research and development costs, there are fewer approved indications, the corresponding patient market is relatively narrow, and pharmaceutical companies need the right price to recover costs and profits.
If manufacturers are forced to sell at low prices, in the long run, pharmaceutical companies and researchers will no longer have the incentive to study new technologies, which is not a good thing for patients in the long run.
In addition, there are medical insurance, patent licensing, etc., many factors will affect the price of drugs.
Will the price of CAR-T cell therapy decline in the future?
We believe it will.
At present, we have seen the efforts of many parties, such as preferential schemes given by pharmaceutical companies, commercial insurance, and more and more drugs for CAR-T cell therapy, and full competition in the market will reduce drug prices.
In a complex world, many times there is no simple answer.
But we must always have hope, after all, countless efforts are being made silently.
For most people, "no cancer" is still the best way to prevent cancer.
Review expert: Cui Wei
Attending physician of the Department of Interventional Therapy, Cancer Center of Guangdong Provincial People's Hospital
bibliography
[1] Joseph Oved, David Barrett, David Teachey. Cellular therapy: Immune-related complications. Immunol Rev. 2019 Jul;290(1):114-126.
[2] Morello A, Sadelain M, et al. Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors. Cancer Discov. 2016 Feb;6(2):133-46.
[3]https://www.bjcancer.org/Html/News/Articles/12768.html
[4]https://m.thepaper.cn/newsDetail_forward_14265156
[5]https://clinicaltrials.gov/ct2/results?cond=CAR-T
Zhu Jinghan,Liang Yuanzheng,Wang Liang. Challenges and solutions of CAR-T cell therapy[J].Chinese Journal of Cancer Prevention and Control,2021,13(06):594-601.
YO Think Tank. 2021 China CAR-T Industry Research Report.
https://www.iyiou.com/research/20211223951
Author: Luo Tianming, Zhang Xiaoyi
Editors: Zhang Xiaoyi, Zhang Jie, Ye Zhengxing
Proofreading: Wu Yihe | Typesetting: Li Yongmin
Operation: Han Ningning | Coordinator: Wu Wei