“One injection of 1.2 million yuan can make cancer cells disappear”.
Not long ago, many people were swiped by this news.
The therapy in the news is a CAR-T therapy.
On June 22, 2021, China approved the launch of the first CAR-T cell therapy drug (a method of tumor immunotherapy). Recently, the official price of the injection was released, just as previously guessed – 1.2 million yuan per injection.
At this price, it is not an exaggeration to say that it is a “high-priced drug”.
This has made many people think: If you unfortunately get cancer, CAR-T therapy needs 1.2 million, is it worth it?
If it were you, what would you choose?
This is not an easy question.
Life is priceless, but after the unfortunate illness, treatment costs money.
Different people have different answers to this question.
But before answering, it’s critical to be clear about these few questions.
What exactly can CAR-T therapy do? Which cancer patients is it effective for? 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 a type of immunotherapy. The so-called immunotherapy is to increase the lethality of immune cells in the body. The immune cells are equipped with directional missiles to directly target tumor cells and kill them accurately [1].
We know that tumor cells are “traitors” of human cells. Normal cells in the human body undergo a series of genetic mutations and become uncontrolled and infinitely growing mutant 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 most of them are hunted down by the immune system. Cancer cells can escape the pursuit of the immune system by disguising and inhibiting the function of immune cells, and grow and reproduce under the eyes of the immune system.
Immunotherapy specifically targets this superpower.
The process goes like this:
1. The hospital collects blood, separates immune T cells from the blood, and reinfuses the remaining blood into the patient;
2. Send the isolated T cells to the laboratory or factory;
3.Modification: Through genetic engineering, T cells are equipped with “targeters” that specifically recognize molecules on the surface of tumor cells, and the modified T body is modified The cells are called CAR-T cells, which have super-strong functions of recognizing and killing tumors;
4.Expansion: The modified CAR-T cells need to be cultured to a certain number in vitro to meet the therapeutic requirements. Therefore, CAR-T cells need to be The cells were extensively expanded in vitro;
5.Reinfusion: CAR-T cells are injected into the patient’s body, and CAR-T cells directly recognize antigens on the surface of tumor cells, thereby killing tumor cells.
The treatment is simple and brief, as blood is drawn from the arm, modified, and delivered back into the body.
This is a shorter cycle than chemotherapy and radiotherapy, and the patient suffers less damage. CAR-T treatment usually requires only 1 or 2 intravenous infusions without repeated administration.
This engineered immune cell is a cancer-fighting “special force” capable of killing specific tumor cells.
It can also self-replicate and expand in the human body, continuously replenishing “casualty attrition”, long-term stationing in the patient’s body, and immune surveillance.
This kind of therapy is more precise. Compared with the side effects of traditional chemotherapy drugs, CAR-T cells can avoid the accidental killing of normal cells and have less side effects.
Immune cell therapy works well, but the publicity in the news is exaggerated.
To sum up, immune cell therapy is effective, but the indications are limited, and it is not suitable for all cancers.
CAR-T cell therapy has only made breakthroughs in some hematological tumors at present, and in the field of solid tumors with a larger proportion of patients, it remains to be seen.Further research and optimization[2].
According to the 2020 International Agency for Research on Cancer, the top 10 cancer types in China are all solid tumors: lung, breast, stomach, colorectal, liver, esophagus Cancer, cervical cancer, thyroid cancer, uterine cancer, prostate cancer [3], that is to say, most Chinese cancer patients are currently unable to use this new treatment method.
But for blood tumors, such as leukemia and lymphoma, the traditional first-line treatment methods are chemotherapy, radiotherapy, and targeted therapy.
Chemotherapy has many disadvantages. Patients will have many adverse reactions (such as vomiting, hair loss, etc.), which are very painful.
In the treatment of refractory and recurrent hematological tumors, the recurrence rate of traditional first-line therapy is high.
According to the data released by the International Agency for Research on Cancer of the World Health Organization, in 2020, there will be about 1.28 million new cases of hematological tumors and 650,000 deaths worldwide;
Hematological tumors have a high recurrence rate after first-line treatment. For example, in patients with diffuse large B-cell lymphoma, after first-line treatment remission, about 30% to 40% will develop drug resistance or relapse [3] ].
After relapse, it means that the original therapy has failed, and it is more difficult to treat again, which ultimately affects the survival rate.
In contrast, CAR-T therapy is suitable for a wide range of people and may prolong the survival time of patients.
Several cases of successful CAR-T cell therapy have been reported.
In July 2019, Aunt Chen was diagnosed with diffuse large B-cell lymphoma (DLBCL). After treatment, her condition was relieved, but the effect was poor after relapse in 2021.
On June 22, 2021, Auntie Chen received Akilence injection (a CATR-T therapy) treatment at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. After two months After receiving treatment, Aunt Chen was evaluated as “completely relieved of symptoms”, and her physical condition was getting better and better, and she was allowed to be discharged from the hospital [4].
The CAR-T products approved this time are based on the clinical trial results released in 2017:
1-year follow-up results: The best overall response rate was 82%, with a complete response rate of 54%.
2-year follow-up results: At a median follow-up of 27.1 months, 39% of subjects were still in remission, and 37% of them were in complete remission .
4-year follow-up results: The median follow-up time was 51.1 months, the 4-year overall survival rate was 44%, and the median survival time (50% of patients survived this time) to 25.8 months [5].
You must know that the patients entering this clinical trial are all patients with “relapsed or refractory” lymphoma, and it is difficult to achieve such a good effect with conventional radiotherapy and chemotherapy.
In 2018, the number of new cancers in my country was 3.8 million, and hematological tumors accounted for about 9.9%, of which about 20% of patients with acute lymphoblastic leukemia were suitable for second-line therapy or less, that is, about 70,000 patients , can benefit from this CAR-T cell therapy.
However, CAR-T cell therapy is not perfect. Currently, it is an individualized therapy with immature production technology and high cost; and some patients still experience relapse after treatment.
In addition, CAR-T cell therapy also has side effects. A study showed that almost all patients who received CD19-targeted CAR-T cell therapy had different degrees of toxic and side effects, such as cytokine release syndrome. Hypoxia and organ failure, etc. [6].
As of January 2022, only two CAR-T cell drugs have been approved for marketing in China, priced at RMB 1.2 million and RMB 1.29 million respectively.
At present, a total of 7 CAR-T cell drugs have been approved for marketing in the world, and the approved indications are also limited to acute lymphoblastic leukemia, multiple myeloma, Hodgkin lymphoma, etc. In the field of hematology and tumor [7], these treatments cost more than one million yuan in China.
All can be described as “astronomical prices”.
Why is CAR-T cell therapy so expensive?
Behind the high price of CAR-T is a complex issue involving many aspects such as medicine, pharmacoeconomics, economics, and medical industry development.
First, CAR-T treatment needs to be customized,It is an individualized drug, which cannot be mass-produced. Each batch of products costs high costs and requires a 2-4 week culture and preparation cycle.
Second, the entire treatment process is very complicated, involving many technical links, and strict quality control requirements. At present, there is no mature and standardized production process in the world, and many links rely on manual operation. , the failure rate is high.
Thirdly, 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 also leads 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, and there are few approved indications, and the corresponding patient market is relatively narrow. The right price is needed to recover the cost as well as make a profit.
If manufacturers are forced to sell at low prices, in the long run, pharmaceutical companies and researchers will no longer have the motivation to study new technologies, which is not good for patients in the long run.
In addition, there are medical insurance, patent licensing, etc., many factors will affect the price of drugs.
Will drug prices for CAR-T cell therapy drop in the future?
We believe it will.
At present, we have seen many efforts, such as preferential plans given by pharmaceutical companies, commercial insurance, and more and more CAR-T cell therapy drugs. Full competition in the market will make Drug prices fell.
In a complex world, there are often no easy answers.
However, we must always have hope, since countless efforts are being made in silence.
And for most people, “no cancer” is still the best way to prevent cancer.
Reviewer: Wei Cui
Attending Physician, MD, Interventional Therapy Department, Cancer Center, Guangdong Provincial People’s Hospital
References
[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.< /p>
[3]https:https://www.bjcancer.org/Html/News/Articles/12768.html
[4]https:https://m.thepaper.cn/newsDetail_forward_14265156
[5]https:https://clinicaltrials.gov/ct2/results?cond=CAR-T
[6] Zhu Jinghan, Liang Yuanzheng, Wang Liang. Challenges and solutions for CAR-T cell therapy [J]. Chinese Journal of Cancer Prevention, 2021, 13(06): 594-601.
[7] Yiou Think Tank. 2021 China CAR-T Industry Research Report.
https: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