-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Chimeric Antigen Receptor T Cell (CAR-T) has become an important treatment for relapsed and refractory non-Hodgkin’s lymphoma (NHL).
CAR-T lymphoma treatment targeting CD19 has been approved in Europe and the United States.
The number of CAR-T clinical trials in China is also parallel to that in the United States.
At the same time, domestic new CAR-T cell research and development and application technology innovation (such as dual-target CAR -T technology, multiple CAR-T sequential therapies, etc.
) are constantly refreshing data, and CAR-T cell lymphoma treatment is just around the corner.
With the deepening of research and the increase in clinical applications, clinicians are paying more and more attention to the toxic and side effects of CAR-T cells and clinical prevention and control measures.
The Biotherapeutics Committee of the Chinese Research Hospital Association organized experts to refer to and learn from the existing CAR-T cytotoxicity management consensus, and at the same time, combined the case reports and clinical treatment experience of 31 CAR-T clinical research institutions in China, and compiled the " The Expert Consensus on Clinical Management of CAR-T Cells to Treat NHL Toxic and Side Effects" aims to provide clinicians with more standardized treatment principles and exploratory treatment suggestions for identifying and handling the toxic and side effects of CAR-T treatment of NHL.
This consensus mainly introduces 4 parts of CAR-T-related toxic and side effects, including cytokine release syndrome (CRS), CAR-T-related encephalopathy syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and other adverse events (Bone marrow suppression, infection, B-cell deficiency/hypogammaglobulinemia, tumor lysis syndrome, allergic reaction, abnormal proliferation of CAR-T cells, etc.
).
In this issue, the editor summarizes the CRS part as follows for the reference of readers.
CRS is a hyperphysiological response caused by the activation of endogenous or infused T cells and other immune cells in the body caused by immunotherapy.
The incidence of CRS related to CAR-T cell therapy in lymphoma cases is 30%-95%, and the incidence of severe CRS (≥G3) is 10%-30%.
Different from acute lymphoblastic leukemia, CAR-T cell therapy-related CRS in lymphoma has specific mechanisms and clinical manifestations.
Refining the stage and classification of CRS will help clinicians to more effectively deal with this adverse event.
Control.
CRS staging and classification according to the time of occurrence CRS can be divided into: ① Acute CRS (onset time: 1 to 3 weeks after CAR-T cell reinfusion); ② Delayed acute CRS (onset time: 3 after CAR-T cell reinfusion) ~6 weeks); ③Chronic CRS (onset time: 6 weeks after CAR-T cell reinfusion).
CRS can be divided into: ①Local-CRS (L-CRS): Local-CRS (L-CRS): After immunotherapy, the inflammatory reaction that appears locally and around the lesion can be manifested by enlarged lesions, local "redness, swelling, heat and pain", There may be exudation or effusion around the lesion, even bleeding, perforation, etc.
; ②Systematic-CRS (Systematic-CRS).
CRS classification standards Table 1 CRS classification standards related to lymphoma CAR-T cell therapy* Low oxygen flow oxygen flow ≤ 6L/min; high oxygen flow oxygen flow ＞ 6L/min; # Venturi inner cover: made according to the Venturi principle , That is, when oxygen enters the mask through the narrow channels, negative pressure is generated around the jet airflow, and a certain amount of air flows into the mask from the open edge.
The size of the side seam of the mask changes the ratio of air to oxygen.
1 to 3 weeks after the reinfusion of acute CRSCAR-T cells (acute CRS stage) is the time period with the highest incidence of CRS and severe CRS, and is also a critical period for treatment.
According to clinical manifestations, the changes in the proliferation and distribution of CAR-T cells in the acute CRS stage can be divided into 4 periods: CAR-T cell local expansion period (1～5d after CAR-T cell reinfusion); CAR-T cell Spillover period (5-10 days after CAR-T cell reinfusion); CAR-T cell redistribution period (10-15 days after CAR-T cell reinfusion); Recovery period (15-21 days after CAR-T cell reinfusion).
Physical examination and monitoring during acute CRS ① Physical examination of the lymphoma lesion site: lesion size, texture, local temperature, tenderness; lymphoma involves important organs, attention should be paid to changes in the signs of the affected organs, such as pulmonary lymphoma, attention should be paid to breathing Sound, lower lung boundary (effusion sign), etc.
; ② Whole body examination: vital signs, skin and mucous membranes, chest, abdomen, nervous system, etc.
; ③ After CAR-T cell reinfusion, check the body at least twice a day until CRS drops Level 1; ④It is recommended to start ECG monitoring with CAR-T cell reinfusion; ⑤ECG monitoring items: heart rate, respiration, blood pressure, blood oxygen saturation; ⑥When CRS drops to level 1, you can consider stopping monitor monitoring; ⑦" "High-risk cases" ECG monitoring: It is recommended to start with the cell reinfusion until 3 weeks after the reinfusion or the high-risk factors are removed; ⑧CRS patients with grades 3 to 4 should be transferred to ICU for monitoring and treatment.
Laboratory examination and special examination during acute CRS.
Laboratory examination item recommendations: blood routine (recommended application); blood biochemistry (liver and kidney function, triglycerides, lactate dehydrogenase, myocardial enzymes and electrolytes, etc.
) (recommended application); Coagulation function test (recommended application): arterial blood gas analysis (recommended application); infection-related test: procalcitonin (recommended application); serum endotoxin (recommended trial application); G/GM-test (recommended trial application); cell Factor monitoring items: CRP (recommended application); IL-6 (recommended application); IL-1 (recommended trial application); IL-2 (recommended trial application); IL-15 (recommended trial application); TNF-α (recommended application) Try to apply); IFN-α (recommended to try); IFN-γ (recommended to try); CAR-T cell detection: CAR gene quantitative PCR detection (recommended); Peripheral blood CAR-T cell flow cytometry (recommended to try application).
Testing frequency of laboratory items: (recommended to try application) ① Check items before CAR-T cell reinfusion (1 "Baseline Inspection and Risk Assessment"), on the 3rd day after reinfusion (d3), d7, d10, d14, d21, d28 , 3 months, 6 months, 9 months, 12 months after reinfusion; ②High-risk cases should be tested every 2 to 3 days after reinfusion; ③When the condition changes, the test items and frequency shall be determined by the clinician.
Special examination points: (recommended to try and apply) ①The principle of selection of special examination items: Evaluation of lymphoma lesions and changes in involved organs (L-CRS), and functional evaluation of the organs involved in SCRS; ②The examination items and frequency reference are determined by the clinician .
The clinical grading treatment strategy of acute CRS The clinical treatment of CRS includes monitoring and treatment.
According to the severity (grading) of CRS, different intensity monitoring modes and treatment strategies are adopted (Table 2).
Table 2 Monitoring modes and treatment strategies of different CRS severity levels The maximum single treatment dose of tocilizumab is 800 mg (recommended application); if necessary, tocilizumab can be repeated after 6 hours.
After the treatment measures are implemented, observe 24h CRS symptoms without improvement or aggravation, should be upgraded to the next level of treatment (recommended trial application); high-risk cases observed 12h CRS symptoms after treatment without improvement or aggravation, should be upgraded to the next level of treatment (recommended trial application ); high-risk diseases such as no contraindications to β-blockers, it is recommended to give β-blockers immediately after CAR-T cell reinfusion (Metoprolol tartrate tablets 12.
5～25mg orally once every 12h) (recommended to try application).
Symptomatic supportive treatment of acute CRSSymptomatic supportive treatment runs through the treatment of all levels of CRS.
This article mainly introduces the recommended treatment for fever, hypotension, and hypoxemia.
Fever: Physical cooling and non-steroidal antipyretic treatment are mainly recommended.
Hypotension (systolic blood pressure <90mmHg): quickly add 500～1000mL of 0.
9% normal saline; if blood pressure does not recover, give colloidal rehydration, such as hydroxyethyl starch injection 500mL intravenous drip, or albumin injection (0.
25～0.
4g /kg) intravenous infusion; if the blood pressure still does not recover, give 1 vasoactive drug; if there is no improvement, multiple vasoactive drugs are combined for treatment.
The dose of vasoactive drugs such as dopamine ranges from 2 to 20 μg (min·kg), and the dose is gradually increased; The initial dose of norepinephrine is 2μg/min, gradually increase; the initial dose of epinephrine is 2μg/min, gradually increase. Hypoxemia: low-flow nasal cannula for oxygen inhalation, oxygen flow ≤ 6L/min; hypoxemia is not corrected, high oxygen flow (oxygen flow ＞ 6L/min) nasal cannula, or face mask, or venturi inhalation of oxygen, Hypoxemia has not been corrected, and positive pressure ventilation assisted breathing (noninvasive mechanical ventilation, or endotracheal intubation mechanical ventilation) is given after the respiratory department consultation.
During acute CRS, lymphomas of different organs are involved in the treatment of local cytokine release syndrome (L-CRS).
It is recommended that lymphomas can affect all organs of the body, so the treatment of L-CRS in different parts has its particularity.
This consensus summarizes existing literature and multi-center clinical research experience.
The recommendations for the treatment of L-CRS in different parts are as follows: Pulmonary parenchymal involvement: Level 2 to 3 L-CRS preferentially select IL-6 receptor antagonists (such as tocilizumab) 4～8mg/kg intravenous infusion) (recommended application).
Massive intra-abdominal lesions (maximum diameter ≥10cm): pretreatment starts with induction and management (protective isolation, food sterilization) according to the transplantation model (recommended trial application); treatment of intestinal flora adjustment (pretreatment starts oral intestinal intestines) Probiotics, such as clostridium butyricum triple viable tablets orally) (recommended for trial application); cell reinfusion d3, d5 for preventive TNF-α antibody therapy (recommended trial application); for L-CRS of level 2 to 3, preferred Combination therapy with antibodies that block the TNF-α pathway is the main treatment (recommended for trial application).
Serous cavity lymphoma is involved, resulting in medium and large serous cavity effusion: puncture and drainage of serous cavity effusion before CAR-T cell reinfusion (recommended trial application); indwelling serous cavity drainage tube until CRS is corrected (recommended trial application) 3 to 5 days before CAR-T cell reinfusion, tocilizumab 80mg is injected locally in the serosal cavity (recommended for trial application).
Cardiac involvement: The cardiology specialist evaluates possible adverse events (arrhythmia, heart failure, myocardial damage, etc.
) (recommended trial application); it is recommended to give non-CAR-T treatment to clear the heart disease, and then consider CAR-T cell therapy (recommended trial application).
Skin, muscle, and connective tissue involvement: before CAR-T cell therapy, reduce or clear skin and soft tissue lesions (try application recommended); strengthen the prevention of local skin infections (topical medication, debridement, etc.
) (recommended trial application); CAR-T Early empirical anti-infective therapy after cell reinfusion (recommended to try and apply). Central nervous system involvement: neurology specialist evaluation (recommended trial application); curative effect is not yet clear, high risk, carefully choose CAR-T cell therapy (recommended trial application).
Swallowing dysfunction caused by compression of neck lesions: fasting, indwelling gastric tube nasal feeding, avoiding aspiration (recommended application); bridging therapy or intensive pretreatment, as far as possible to relieve symptoms of compression before reinfusion (recommended trial application).
Difficulty breathing caused by compression of cervical lesions: fasting, indwelling gastric tube and nasal feeding to avoid aspiration (recommended application); bridging therapy or intensive pretreatment, as far as possible to relieve symptoms of compression before reinfusion (recommended trial application); develop emergency tracheal intubation Pre-plan, conventional bedside equipped with tracheostomy package (recommended to try application).
Delayed acute CRS The definition, clinical manifestations and differential diagnosis of delayed acute CRS.
The clinical manifestations are mainly systemic CRS, which is the delay and lag of acute CRS, which occurs 3～3 after CAR-T cell reinfusion.
6 weeks.
Clinical manifestations of late-onset acute CRS: fever; three-line peripheral blood decline, mostly due to thrombocytopenia; some patients are accompanied by abnormal elevation of transaminase; abnormal blood coagulation indicators; peripheral blood detection of CAR copy number increases; patients have not reached completeness Remission, there are still tumors remaining.
Delayed acute CRS should be differentiated from hematological toxicity, adverse digestive events, and infection caused by pretreatment (chemotherapeutics).
Physical examination, laboratory examination and special examination for the treatment of delayed acute CRS: It is recommended to refer to acute CRS.
Treatment advice: Refer to acute CRS for treatment.
Chronic CRS The definition, clinical manifestations and differential diagnosis of chronic CRS Chronic CRS refers to inflammatory-related or CAR-T cell reinfusion-related adverse events that occur ≥ 6 weeks after the reinfusion of CAR-T cells.
Clinical manifestations of chronic CRS: slow onset or persistent presence; intermittent low fever (below 38°C); fatigue, anorexia; peripheral blood three-line decline, mostly mainly due to thrombocytopenia; clear presence of CAR copy number or CAR in peripheral blood -The proportion of T cell flow cytometry has risen again; tumor remains, and a small number of patients with chest CT show lung interstitial inflammation-like features, or bronchiectasis-like features.
Chronic CRS should be differentiated from infection and hematological toxicity after CAR-T cell therapy.
Treatment of chronic CRS, symptomatic and supportive treatment, TNF-α/TNF-αR inhibitors, such as etanercept (25-50 mg), or infliximab 3-5 mg/kg for injection, are beneficial to improve pulmonary symptoms; monitor blood routine , If necessary, give blood component transfusion supportive treatment.
This article is excerpted from the Biotherapeutics Committee of the Chinese Research Hospital Association.
Expert consensus on the clinical management of the toxic and side effects of CAR T cell treatment of NHL[J].
Journal of Translational Medicine,2021,10(1):1-11.
Please contact us if you encounter copyright issues delete.
Poke "read the original text" and we will make progress together
CAR-T lymphoma treatment targeting CD19 has been approved in Europe and the United States.
The number of CAR-T clinical trials in China is also parallel to that in the United States.
At the same time, domestic new CAR-T cell research and development and application technology innovation (such as dual-target CAR -T technology, multiple CAR-T sequential therapies, etc.
) are constantly refreshing data, and CAR-T cell lymphoma treatment is just around the corner.
With the deepening of research and the increase in clinical applications, clinicians are paying more and more attention to the toxic and side effects of CAR-T cells and clinical prevention and control measures.
The Biotherapeutics Committee of the Chinese Research Hospital Association organized experts to refer to and learn from the existing CAR-T cytotoxicity management consensus, and at the same time, combined the case reports and clinical treatment experience of 31 CAR-T clinical research institutions in China, and compiled the " The Expert Consensus on Clinical Management of CAR-T Cells to Treat NHL Toxic and Side Effects" aims to provide clinicians with more standardized treatment principles and exploratory treatment suggestions for identifying and handling the toxic and side effects of CAR-T treatment of NHL.
This consensus mainly introduces 4 parts of CAR-T-related toxic and side effects, including cytokine release syndrome (CRS), CAR-T-related encephalopathy syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and other adverse events (Bone marrow suppression, infection, B-cell deficiency/hypogammaglobulinemia, tumor lysis syndrome, allergic reaction, abnormal proliferation of CAR-T cells, etc.
).
In this issue, the editor summarizes the CRS part as follows for the reference of readers.
CRS is a hyperphysiological response caused by the activation of endogenous or infused T cells and other immune cells in the body caused by immunotherapy.
The incidence of CRS related to CAR-T cell therapy in lymphoma cases is 30%-95%, and the incidence of severe CRS (≥G3) is 10%-30%.
Different from acute lymphoblastic leukemia, CAR-T cell therapy-related CRS in lymphoma has specific mechanisms and clinical manifestations.
Refining the stage and classification of CRS will help clinicians to more effectively deal with this adverse event.
Control.
CRS staging and classification according to the time of occurrence CRS can be divided into: ① Acute CRS (onset time: 1 to 3 weeks after CAR-T cell reinfusion); ② Delayed acute CRS (onset time: 3 after CAR-T cell reinfusion) ~6 weeks); ③Chronic CRS (onset time: 6 weeks after CAR-T cell reinfusion).
CRS can be divided into: ①Local-CRS (L-CRS): Local-CRS (L-CRS): After immunotherapy, the inflammatory reaction that appears locally and around the lesion can be manifested by enlarged lesions, local "redness, swelling, heat and pain", There may be exudation or effusion around the lesion, even bleeding, perforation, etc.
; ②Systematic-CRS (Systematic-CRS).
CRS classification standards Table 1 CRS classification standards related to lymphoma CAR-T cell therapy* Low oxygen flow oxygen flow ≤ 6L/min; high oxygen flow oxygen flow ＞ 6L/min; # Venturi inner cover: made according to the Venturi principle , That is, when oxygen enters the mask through the narrow channels, negative pressure is generated around the jet airflow, and a certain amount of air flows into the mask from the open edge.
The size of the side seam of the mask changes the ratio of air to oxygen.
1 to 3 weeks after the reinfusion of acute CRSCAR-T cells (acute CRS stage) is the time period with the highest incidence of CRS and severe CRS, and is also a critical period for treatment.
According to clinical manifestations, the changes in the proliferation and distribution of CAR-T cells in the acute CRS stage can be divided into 4 periods: CAR-T cell local expansion period (1～5d after CAR-T cell reinfusion); CAR-T cell Spillover period (5-10 days after CAR-T cell reinfusion); CAR-T cell redistribution period (10-15 days after CAR-T cell reinfusion); Recovery period (15-21 days after CAR-T cell reinfusion).
Physical examination and monitoring during acute CRS ① Physical examination of the lymphoma lesion site: lesion size, texture, local temperature, tenderness; lymphoma involves important organs, attention should be paid to changes in the signs of the affected organs, such as pulmonary lymphoma, attention should be paid to breathing Sound, lower lung boundary (effusion sign), etc.
; ② Whole body examination: vital signs, skin and mucous membranes, chest, abdomen, nervous system, etc.
; ③ After CAR-T cell reinfusion, check the body at least twice a day until CRS drops Level 1; ④It is recommended to start ECG monitoring with CAR-T cell reinfusion; ⑤ECG monitoring items: heart rate, respiration, blood pressure, blood oxygen saturation; ⑥When CRS drops to level 1, you can consider stopping monitor monitoring; ⑦" "High-risk cases" ECG monitoring: It is recommended to start with the cell reinfusion until 3 weeks after the reinfusion or the high-risk factors are removed; ⑧CRS patients with grades 3 to 4 should be transferred to ICU for monitoring and treatment.
Laboratory examination and special examination during acute CRS.
Laboratory examination item recommendations: blood routine (recommended application); blood biochemistry (liver and kidney function, triglycerides, lactate dehydrogenase, myocardial enzymes and electrolytes, etc.
) (recommended application); Coagulation function test (recommended application): arterial blood gas analysis (recommended application); infection-related test: procalcitonin (recommended application); serum endotoxin (recommended trial application); G/GM-test (recommended trial application); cell Factor monitoring items: CRP (recommended application); IL-6 (recommended application); IL-1 (recommended trial application); IL-2 (recommended trial application); IL-15 (recommended trial application); TNF-α (recommended application) Try to apply); IFN-α (recommended to try); IFN-γ (recommended to try); CAR-T cell detection: CAR gene quantitative PCR detection (recommended); Peripheral blood CAR-T cell flow cytometry (recommended to try application).
Testing frequency of laboratory items: (recommended to try application) ① Check items before CAR-T cell reinfusion (1 "Baseline Inspection and Risk Assessment"), on the 3rd day after reinfusion (d3), d7, d10, d14, d21, d28 , 3 months, 6 months, 9 months, 12 months after reinfusion; ②High-risk cases should be tested every 2 to 3 days after reinfusion; ③When the condition changes, the test items and frequency shall be determined by the clinician.
Special examination points: (recommended to try and apply) ①The principle of selection of special examination items: Evaluation of lymphoma lesions and changes in involved organs (L-CRS), and functional evaluation of the organs involved in SCRS; ②The examination items and frequency reference are determined by the clinician .
The clinical grading treatment strategy of acute CRS The clinical treatment of CRS includes monitoring and treatment.
According to the severity (grading) of CRS, different intensity monitoring modes and treatment strategies are adopted (Table 2).
Table 2 Monitoring modes and treatment strategies of different CRS severity levels The maximum single treatment dose of tocilizumab is 800 mg (recommended application); if necessary, tocilizumab can be repeated after 6 hours.
After the treatment measures are implemented, observe 24h CRS symptoms without improvement or aggravation, should be upgraded to the next level of treatment (recommended trial application); high-risk cases observed 12h CRS symptoms after treatment without improvement or aggravation, should be upgraded to the next level of treatment (recommended trial application ); high-risk diseases such as no contraindications to β-blockers, it is recommended to give β-blockers immediately after CAR-T cell reinfusion (Metoprolol tartrate tablets 12.
5～25mg orally once every 12h) (recommended to try application).
Symptomatic supportive treatment of acute CRSSymptomatic supportive treatment runs through the treatment of all levels of CRS.
This article mainly introduces the recommended treatment for fever, hypotension, and hypoxemia.
Fever: Physical cooling and non-steroidal antipyretic treatment are mainly recommended.
Hypotension (systolic blood pressure <90mmHg): quickly add 500～1000mL of 0.
9% normal saline; if blood pressure does not recover, give colloidal rehydration, such as hydroxyethyl starch injection 500mL intravenous drip, or albumin injection (0.
25～0.
4g /kg) intravenous infusion; if the blood pressure still does not recover, give 1 vasoactive drug; if there is no improvement, multiple vasoactive drugs are combined for treatment.
The dose of vasoactive drugs such as dopamine ranges from 2 to 20 μg (min·kg), and the dose is gradually increased; The initial dose of norepinephrine is 2μg/min, gradually increase; the initial dose of epinephrine is 2μg/min, gradually increase. Hypoxemia: low-flow nasal cannula for oxygen inhalation, oxygen flow ≤ 6L/min; hypoxemia is not corrected, high oxygen flow (oxygen flow ＞ 6L/min) nasal cannula, or face mask, or venturi inhalation of oxygen, Hypoxemia has not been corrected, and positive pressure ventilation assisted breathing (noninvasive mechanical ventilation, or endotracheal intubation mechanical ventilation) is given after the respiratory department consultation.
During acute CRS, lymphomas of different organs are involved in the treatment of local cytokine release syndrome (L-CRS).
It is recommended that lymphomas can affect all organs of the body, so the treatment of L-CRS in different parts has its particularity.
This consensus summarizes existing literature and multi-center clinical research experience.
The recommendations for the treatment of L-CRS in different parts are as follows: Pulmonary parenchymal involvement: Level 2 to 3 L-CRS preferentially select IL-6 receptor antagonists (such as tocilizumab) 4～8mg/kg intravenous infusion) (recommended application).
Massive intra-abdominal lesions (maximum diameter ≥10cm): pretreatment starts with induction and management (protective isolation, food sterilization) according to the transplantation model (recommended trial application); treatment of intestinal flora adjustment (pretreatment starts oral intestinal intestines) Probiotics, such as clostridium butyricum triple viable tablets orally) (recommended for trial application); cell reinfusion d3, d5 for preventive TNF-α antibody therapy (recommended trial application); for L-CRS of level 2 to 3, preferred Combination therapy with antibodies that block the TNF-α pathway is the main treatment (recommended for trial application).
Serous cavity lymphoma is involved, resulting in medium and large serous cavity effusion: puncture and drainage of serous cavity effusion before CAR-T cell reinfusion (recommended trial application); indwelling serous cavity drainage tube until CRS is corrected (recommended trial application) 3 to 5 days before CAR-T cell reinfusion, tocilizumab 80mg is injected locally in the serosal cavity (recommended for trial application).
Cardiac involvement: The cardiology specialist evaluates possible adverse events (arrhythmia, heart failure, myocardial damage, etc.
) (recommended trial application); it is recommended to give non-CAR-T treatment to clear the heart disease, and then consider CAR-T cell therapy (recommended trial application).
Skin, muscle, and connective tissue involvement: before CAR-T cell therapy, reduce or clear skin and soft tissue lesions (try application recommended); strengthen the prevention of local skin infections (topical medication, debridement, etc.
) (recommended trial application); CAR-T Early empirical anti-infective therapy after cell reinfusion (recommended to try and apply). Central nervous system involvement: neurology specialist evaluation (recommended trial application); curative effect is not yet clear, high risk, carefully choose CAR-T cell therapy (recommended trial application).
Swallowing dysfunction caused by compression of neck lesions: fasting, indwelling gastric tube nasal feeding, avoiding aspiration (recommended application); bridging therapy or intensive pretreatment, as far as possible to relieve symptoms of compression before reinfusion (recommended trial application).
Difficulty breathing caused by compression of cervical lesions: fasting, indwelling gastric tube and nasal feeding to avoid aspiration (recommended application); bridging therapy or intensive pretreatment, as far as possible to relieve symptoms of compression before reinfusion (recommended trial application); develop emergency tracheal intubation Pre-plan, conventional bedside equipped with tracheostomy package (recommended to try application).
Delayed acute CRS The definition, clinical manifestations and differential diagnosis of delayed acute CRS.
The clinical manifestations are mainly systemic CRS, which is the delay and lag of acute CRS, which occurs 3～3 after CAR-T cell reinfusion.
6 weeks.
Clinical manifestations of late-onset acute CRS: fever; three-line peripheral blood decline, mostly due to thrombocytopenia; some patients are accompanied by abnormal elevation of transaminase; abnormal blood coagulation indicators; peripheral blood detection of CAR copy number increases; patients have not reached completeness Remission, there are still tumors remaining.
Delayed acute CRS should be differentiated from hematological toxicity, adverse digestive events, and infection caused by pretreatment (chemotherapeutics).
Physical examination, laboratory examination and special examination for the treatment of delayed acute CRS: It is recommended to refer to acute CRS.
Treatment advice: Refer to acute CRS for treatment.
Chronic CRS The definition, clinical manifestations and differential diagnosis of chronic CRS Chronic CRS refers to inflammatory-related or CAR-T cell reinfusion-related adverse events that occur ≥ 6 weeks after the reinfusion of CAR-T cells.
Clinical manifestations of chronic CRS: slow onset or persistent presence; intermittent low fever (below 38°C); fatigue, anorexia; peripheral blood three-line decline, mostly mainly due to thrombocytopenia; clear presence of CAR copy number or CAR in peripheral blood -The proportion of T cell flow cytometry has risen again; tumor remains, and a small number of patients with chest CT show lung interstitial inflammation-like features, or bronchiectasis-like features.
Chronic CRS should be differentiated from infection and hematological toxicity after CAR-T cell therapy.
Treatment of chronic CRS, symptomatic and supportive treatment, TNF-α/TNF-αR inhibitors, such as etanercept (25-50 mg), or infliximab 3-5 mg/kg for injection, are beneficial to improve pulmonary symptoms; monitor blood routine , If necessary, give blood component transfusion supportive treatment.
This article is excerpted from the Biotherapeutics Committee of the Chinese Research Hospital Association.
Expert consensus on the clinical management of the toxic and side effects of CAR T cell treatment of NHL[J].
Journal of Translational Medicine,2021,10(1):1-11.
Please contact us if you encounter copyright issues delete.
Poke "read the original text" and we will make progress together
