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Every coin has two sides.
The miracle is like immunotherapy.
Like any drug we know, it will be accompanied by the risk of side effects while exerting a therapeutic effect.
A research team from the Cleveland Medical Center in the United States recently published a study confirming that among cancer patients treated with immunotherapy, the incidence of individual venous thromboembolism (VTE) is as high as 24% [1], based on which they also believe that venous thrombosis should be treated.
Embolism is managed as a common immune-related adverse event in immunotherapy.
The research results were published in Med, a journal under Cell.
▲ Screenshot of the homepage of the paper.
The side effects of immune checkpoint inhibitors are not the same as conventional chemotherapy drugs.
This is related to the principle of PD-1 inhibitors' efficacy.
The PD-L1 on the cell surface is like our "health code", and the "scanner" in the hands of activated T cells, that is, PD-1, can identify these "health codes" to avoid accidentally injuring normal cells.
Not only do normal cells have a "health code", tumor cells can also express PD-L1, thereby avoiding the killing effect of effector T cells.
The role of PD-1 inhibitors for cancer treatment is to enhance immune function by destroying these "scanners" and blocking immune checkpoints.
But is the immune system really so well controlled? Will the activated immune system "six relatives not recognize"? The answer is yes.
While enhancing tumor-specific immunity, the homeostasis of the immune system is also destroyed, leading to immune-related adverse reactions (irAE).
The irAE here is not only derived from the killing of normal cells by T cells after the ban has been lifted.
The increase in the number of humoral immunity, cytokines, or autoantibodies will all cause adverse reactions in immune-related organs to varying degrees. If you have heard of autoimmune diseases, you should know that this is also a disease caused by the over-activation of the immune system.
Will these immune-related side effects be similar? Indeed, the symptoms of currently known immune-related adverse reactions are indeed similar to autoimmune diseases, including pituitary inflammation, colitis, and skin rashes, but the extent of occurrence is generally relatively mild.
However, the situation of cancer patients is so complicated, will there be adverse reactions beyond our cognition? This Cleveland Medical Center study reveals the "hidden corner" of immunotherapy.
The term venous thromboembolism (VTE) may be familiar to everyone.
The recent frequent reports of the suspension of the use of AstraZeneca's new crown vaccine are because of this VTE, which shows its high risk.
The risk of VTE in cancer patients is 1%-11%, which is 6 times that of non-cancer patients.
What is even more shocking is that thrombosis is the second leading cause of death in cancer patients after the tumor itself! In the treatment of cancer patients, many factors can lead to the occurrence of VTE.
Systemic chemotherapy can increase the risk of thrombosis by 2-6 times.
The central venous catheter that helps patients with intravenous infusion also increases the risk of VTE.
Some cancer treatment drugs include Vascular endothelial growth factor inhibitors, etc.
will increase the risk of thrombosis [2].
So today, as the status of immunotherapy is gradually rising, has anyone studied the relationship between immunotherapy and VTE? Yes, but very few, and the sample size of the study is relatively limited.
Such a research direction to be developed has attracted the attention of the Cleveland Medical Center research team.
The research team’s thinking is very clear.
First of all, they need a larger sample size so that they can be distinguished from the published small sample research and get more convincing conclusions.
Second, they only get the correlation between immunotherapy and thrombosis.
They still need to confirm that venous thromboembolism is indeed an immune-related adverse reaction.
Finally, the so-called predecessors planted trees and future generations enjoy the shade.
If they want to pave the way for follow-up research, find some relevant biomarkers to use Predicting the risk of thrombosis would be a good choice.
Without further ado, let us take a closer look at their research process.
The researchers included 1686 cancer patients receiving immunotherapy, of which 49.
6% were lung cancer patients, 13.
2% were melanoma patients, and 90.
3% of all patients had cancer metastasis.
Among these patients, the most received treatment with Navulizumab, followed by Pembrolizumab and Atelizumab [1].
▲Patients' basic characteristics.
Patients included in this study are basically treated in accordance with the current guidelines recommended scheme, that is, immunotherapy.
This has advantages and disadvantages for this retrospective study.
The advantage is that although the patient’s combined chemotherapy data is not collected, since the treatment is standardized according to the guidelines, the influence of chemotherapy on the results of this trial can be ruled out; the disadvantage is also obvious, that is, there is no control and there is no way to include similar illnesses.
Of patients who do not use immunotherapy to conduct a comparative study.
It was found that among the 1686 patients who received immunotherapy, 404 (24%) had VTE.
Among VTE patients, deep vein thrombosis (DVT) occurred in 42.
6% (n=172), pulmonary embolism (PE) occurred in 33.
2% (n=134), 15.
3% combined DVT and PE (n=63), and 5.
4% occurred Visceral vein thrombosis (VVT) (n=24).
There was no difference in the occurrence of venous thrombosis in individuals receiving different immunotherapy, and in patients receiving combined immunotherapy (mainly nivolumab + ipilimumab), there was also no difference in the occurrence of venous thrombosis.
The difference in the risk of thrombosis between [1].
▲ Proportion of different forms of thrombus So, what clinical factors can help us predict VTE? In univariate analysis, researchers found that age, tumor stage, and cancer metastasis were significantly related to VTE; in multivariate analysis, the range of significant factors affecting VTE narrowed, and only age at first diagnosis and whether cancer metastasis was significantly related to VTE .
In addition to the analysis of the correlation between the basic conditions of these patients and VTE, did the researchers not think about studying the correlation between the remaining irAE and VTE? Researchers have certainly thought about it, but they can only think about it, because irAE occurs frequently in immunotherapy patients.
This is another retrospective analysis, which limits the researcher's possibility of correlation analysis.
The follow-up time for this study was extended, from 7 days to 1971 days, which was nearly 6 years, and the researchers were able to collect overall survival data.
The median survival time of this group of 1686 patients was 416 days.
In patients with VTE, this number was reduced to 365 days.
Compared with 453 days in patients without VTE, VTE has a real impact on the survival of immunotherapy patients.
Is great.
At the same time, a multi-factor risk analysis was performed on overall survival, and it was found that VTE, tumor metastasis, old age, and single-agent immunotherapy would significantly reduce the overall survival rate of patients [1].
▲ The overall survival of VTE patients is better.
There are only three points here, immunotherapy, thrombosis, and survival.
Specifically, immunotherapy patients have a high risk of thrombosis, and immunotherapy patients with thrombosis have a short survival time.
There is still a key point that remains unresolved.
Is VTE an immune-related adverse reaction? To clarify this point, it is necessary to analyze the patient's immune status.
The easiest and most feasible method is to collect blood.
There is a significant correlation between conventional irAE and inflammatory response, and the inflammatory response can be seen in the blood.
The researchers took the peripheral blood mononuclear cells of 25 patients from the cohort (including 7 cases of bladder cancer, 6 cases of renal cell carcinoma, 8 cases of melanoma, and 4 cases of lung cancer).
Among these 25 patients, there were subsequent VTE occurred in 15 people.
▲ Looking for the characteristics of patients with biomarkers.
As far as peripheral blood mononuclear cells are concerned, compared with patients with subsequent VTE and patients without VTE, patients with subsequent VTE have significantly higher myeloid-derived suppressor cells (MDSCs).
MDSCs are derived from bone marrow A group of heterogeneous cells has the ability to significantly inhibit the response of immune cells, and has been widely studied as a target of immunotherapy. At the same time, the researchers also compared the correlation between the occurrence of VTE and 51 plasma factors or chemokines related to inflammatory damage, and found that the increase of IL-8 (interleukin 8) was significantly related to the occurrence of VTE.
Here is an IL- 8/CSCR1/2 pathway, which is also an immune-related pathway.
(MDSCs and IL-8, follow-up research also has a starting point.
After all, translational medicine from clinical to basic is the general trend) After studying here, we can find the correlation between the occurrence of VTE and inflammatory response in immunotherapy.
The VTE biology involved here The markers are completely different from the D-dimer and other indicators used to judge VTE in the past chemotherapy, and they are all immune-related indicators, which further proves that VTE should be managed as an immune-related adverse reaction.
As immunotherapy continues to advance, its advantages and disadvantages will gradually become prominent.
However, the occurrence of adverse reactions is not a reason for injecting rats.
For clinical decision-making, the interests of patients are the first consideration.
How to balance patient benefits and risks is an eternal topic in cancer treatment.
I believe that our scientific researchers and clinicians will bring more and more effective solutions! Singularity is hiring everyone! Everybody Hi~! We need fresh blood to inject new energy into the singularity.
Come on, become the singularity cake and do a new job with us! These are the little friends we are currently looking for~ If you want to create and innovate with the singularity cakes, come join us.
Please send your resume and work (if any) to: hr@geekheal.
com or you can directly add to the WeChat (geekheal-xintan) of Geekheal-xintan for communication.
When adding friends, please note: recruitment + position + professional field.
We are waiting for you at Singularity.
References: [1] Roopkumar J, Swaidani S, Kim AS, et al.
Increased incidence of venous thromboembolism with cancer immunotherapy.
2021.
[2] Donnellan E, AA Khorana.
Cancer and Venous Thromboembolic Disease: A Review[J].
The Oncologist, 2017, 22(2).
Editor in chargeBioTalker
The miracle is like immunotherapy.
Like any drug we know, it will be accompanied by the risk of side effects while exerting a therapeutic effect.
A research team from the Cleveland Medical Center in the United States recently published a study confirming that among cancer patients treated with immunotherapy, the incidence of individual venous thromboembolism (VTE) is as high as 24% [1], based on which they also believe that venous thrombosis should be treated.
Embolism is managed as a common immune-related adverse event in immunotherapy.
The research results were published in Med, a journal under Cell.
▲ Screenshot of the homepage of the paper.
The side effects of immune checkpoint inhibitors are not the same as conventional chemotherapy drugs.
This is related to the principle of PD-1 inhibitors' efficacy.
The PD-L1 on the cell surface is like our "health code", and the "scanner" in the hands of activated T cells, that is, PD-1, can identify these "health codes" to avoid accidentally injuring normal cells.
Not only do normal cells have a "health code", tumor cells can also express PD-L1, thereby avoiding the killing effect of effector T cells.
The role of PD-1 inhibitors for cancer treatment is to enhance immune function by destroying these "scanners" and blocking immune checkpoints.
But is the immune system really so well controlled? Will the activated immune system "six relatives not recognize"? The answer is yes.
While enhancing tumor-specific immunity, the homeostasis of the immune system is also destroyed, leading to immune-related adverse reactions (irAE).
The irAE here is not only derived from the killing of normal cells by T cells after the ban has been lifted.
The increase in the number of humoral immunity, cytokines, or autoantibodies will all cause adverse reactions in immune-related organs to varying degrees. If you have heard of autoimmune diseases, you should know that this is also a disease caused by the over-activation of the immune system.
Will these immune-related side effects be similar? Indeed, the symptoms of currently known immune-related adverse reactions are indeed similar to autoimmune diseases, including pituitary inflammation, colitis, and skin rashes, but the extent of occurrence is generally relatively mild.
However, the situation of cancer patients is so complicated, will there be adverse reactions beyond our cognition? This Cleveland Medical Center study reveals the "hidden corner" of immunotherapy.
The term venous thromboembolism (VTE) may be familiar to everyone.
The recent frequent reports of the suspension of the use of AstraZeneca's new crown vaccine are because of this VTE, which shows its high risk.
The risk of VTE in cancer patients is 1%-11%, which is 6 times that of non-cancer patients.
What is even more shocking is that thrombosis is the second leading cause of death in cancer patients after the tumor itself! In the treatment of cancer patients, many factors can lead to the occurrence of VTE.
Systemic chemotherapy can increase the risk of thrombosis by 2-6 times.
The central venous catheter that helps patients with intravenous infusion also increases the risk of VTE.
Some cancer treatment drugs include Vascular endothelial growth factor inhibitors, etc.
will increase the risk of thrombosis [2].
So today, as the status of immunotherapy is gradually rising, has anyone studied the relationship between immunotherapy and VTE? Yes, but very few, and the sample size of the study is relatively limited.
Such a research direction to be developed has attracted the attention of the Cleveland Medical Center research team.
The research team’s thinking is very clear.
First of all, they need a larger sample size so that they can be distinguished from the published small sample research and get more convincing conclusions.
Second, they only get the correlation between immunotherapy and thrombosis.
They still need to confirm that venous thromboembolism is indeed an immune-related adverse reaction.
Finally, the so-called predecessors planted trees and future generations enjoy the shade.
If they want to pave the way for follow-up research, find some relevant biomarkers to use Predicting the risk of thrombosis would be a good choice.
Without further ado, let us take a closer look at their research process.
The researchers included 1686 cancer patients receiving immunotherapy, of which 49.
6% were lung cancer patients, 13.
2% were melanoma patients, and 90.
3% of all patients had cancer metastasis.
Among these patients, the most received treatment with Navulizumab, followed by Pembrolizumab and Atelizumab [1].
▲Patients' basic characteristics.
Patients included in this study are basically treated in accordance with the current guidelines recommended scheme, that is, immunotherapy.
This has advantages and disadvantages for this retrospective study.
The advantage is that although the patient’s combined chemotherapy data is not collected, since the treatment is standardized according to the guidelines, the influence of chemotherapy on the results of this trial can be ruled out; the disadvantage is also obvious, that is, there is no control and there is no way to include similar illnesses.
Of patients who do not use immunotherapy to conduct a comparative study.
It was found that among the 1686 patients who received immunotherapy, 404 (24%) had VTE.
Among VTE patients, deep vein thrombosis (DVT) occurred in 42.
6% (n=172), pulmonary embolism (PE) occurred in 33.
2% (n=134), 15.
3% combined DVT and PE (n=63), and 5.
4% occurred Visceral vein thrombosis (VVT) (n=24).
There was no difference in the occurrence of venous thrombosis in individuals receiving different immunotherapy, and in patients receiving combined immunotherapy (mainly nivolumab + ipilimumab), there was also no difference in the occurrence of venous thrombosis.
The difference in the risk of thrombosis between [1].
▲ Proportion of different forms of thrombus So, what clinical factors can help us predict VTE? In univariate analysis, researchers found that age, tumor stage, and cancer metastasis were significantly related to VTE; in multivariate analysis, the range of significant factors affecting VTE narrowed, and only age at first diagnosis and whether cancer metastasis was significantly related to VTE .
In addition to the analysis of the correlation between the basic conditions of these patients and VTE, did the researchers not think about studying the correlation between the remaining irAE and VTE? Researchers have certainly thought about it, but they can only think about it, because irAE occurs frequently in immunotherapy patients.
This is another retrospective analysis, which limits the researcher's possibility of correlation analysis.
The follow-up time for this study was extended, from 7 days to 1971 days, which was nearly 6 years, and the researchers were able to collect overall survival data.
The median survival time of this group of 1686 patients was 416 days.
In patients with VTE, this number was reduced to 365 days.
Compared with 453 days in patients without VTE, VTE has a real impact on the survival of immunotherapy patients.
Is great.
At the same time, a multi-factor risk analysis was performed on overall survival, and it was found that VTE, tumor metastasis, old age, and single-agent immunotherapy would significantly reduce the overall survival rate of patients [1].
▲ The overall survival of VTE patients is better.
There are only three points here, immunotherapy, thrombosis, and survival.
Specifically, immunotherapy patients have a high risk of thrombosis, and immunotherapy patients with thrombosis have a short survival time.
There is still a key point that remains unresolved.
Is VTE an immune-related adverse reaction? To clarify this point, it is necessary to analyze the patient's immune status.
The easiest and most feasible method is to collect blood.
There is a significant correlation between conventional irAE and inflammatory response, and the inflammatory response can be seen in the blood.
The researchers took the peripheral blood mononuclear cells of 25 patients from the cohort (including 7 cases of bladder cancer, 6 cases of renal cell carcinoma, 8 cases of melanoma, and 4 cases of lung cancer).
Among these 25 patients, there were subsequent VTE occurred in 15 people.
▲ Looking for the characteristics of patients with biomarkers.
As far as peripheral blood mononuclear cells are concerned, compared with patients with subsequent VTE and patients without VTE, patients with subsequent VTE have significantly higher myeloid-derived suppressor cells (MDSCs).
MDSCs are derived from bone marrow A group of heterogeneous cells has the ability to significantly inhibit the response of immune cells, and has been widely studied as a target of immunotherapy. At the same time, the researchers also compared the correlation between the occurrence of VTE and 51 plasma factors or chemokines related to inflammatory damage, and found that the increase of IL-8 (interleukin 8) was significantly related to the occurrence of VTE.
Here is an IL- 8/CSCR1/2 pathway, which is also an immune-related pathway.
(MDSCs and IL-8, follow-up research also has a starting point.
After all, translational medicine from clinical to basic is the general trend) After studying here, we can find the correlation between the occurrence of VTE and inflammatory response in immunotherapy.
The VTE biology involved here The markers are completely different from the D-dimer and other indicators used to judge VTE in the past chemotherapy, and they are all immune-related indicators, which further proves that VTE should be managed as an immune-related adverse reaction.
As immunotherapy continues to advance, its advantages and disadvantages will gradually become prominent.
However, the occurrence of adverse reactions is not a reason for injecting rats.
For clinical decision-making, the interests of patients are the first consideration.
How to balance patient benefits and risks is an eternal topic in cancer treatment.
I believe that our scientific researchers and clinicians will bring more and more effective solutions! Singularity is hiring everyone! Everybody Hi~! We need fresh blood to inject new energy into the singularity.
Come on, become the singularity cake and do a new job with us! These are the little friends we are currently looking for~ If you want to create and innovate with the singularity cakes, come join us.
Please send your resume and work (if any) to: hr@geekheal.
com or you can directly add to the WeChat (geekheal-xintan) of Geekheal-xintan for communication.
When adding friends, please note: recruitment + position + professional field.
We are waiting for you at Singularity.
References: [1] Roopkumar J, Swaidani S, Kim AS, et al.
Increased incidence of venous thromboembolism with cancer immunotherapy.
2021.
[2] Donnellan E, AA Khorana.
Cancer and Venous Thromboembolic Disease: A Review[J].
The Oncologist, 2017, 22(2).
Editor in chargeBioTalker
