tisagenlecleucel

Action and Spectrum

Actions and Spectrum: 

tisagenlecleucel works by genetically altering a patient’s own T cells so that they can identify and combat cancer cells. This process is known as chimeric antigen receptor (CAR) T-cell therapy.

tisagenlecleucel functions by genetically altering a patient’s T-cells to produce a CAR that identifies a particular protein called CD19, which is present on the surface of B-cells.

T-cells are collected from the patient using a procedure called leukapheresis. These altered CAR T-cells can identify and target cancer cells that show CD19 if they are reinfused into the patient. 

Patients with cancers are only eligible for tisagenlecleucel, such as those with recurrences or refractory B-cell ALL who are 25 years old or younger and adult patients with recurrences or refractory DLBCL who have not improved to prior therapies.

tisagenlecleucel is not appropriate for all people with certain forms of cancer, and the eligibility requirements for therapy may change based on the precise malignancy and stage of the illness. 

Drug Interaction

Adverse Reaction

Frequency Defined  

>10% (including all Pediatric & Young Adults) 

Cytokine release syndrome (79%) 

Cytokine release syndrome, grades 3-4 (49%) 

Decreased appetite (37%) 

Hypogammaglobulinemia (43%) 

Infection, unspecified pathogen (41%) 

Pyrexia (40%) 

Prolonged neutropenia, Day 28 (40%) 

Febrile neutropenia, grades 3-4 (37%) 

Headache (37%) 

Encephalopathy (34%) 

Hypotension (31%) 

Increased AST, grades 3-4 (28%) 

Hypokalemia, grades 3-4 (27%) 

Prolonged thrombocytopenia, Day 28 (27%) 

Vomiting (26%) 

Viral infection (26%) 

Nausea (26%) 

Diarrhea (26%) 

Tachycardia (26%) 

Fatigue (25%) 

Hypotension, grades 3-4 (22%) 

Edema (21%) 

Cough (21%) 

Hypoxia (24%) 

Acute kidney injury (24%) 

Hypophosphatemia, grades 3-4 (19%) 

Hypertension (19%) 

Increased ALT, grades 3-4 (21%) 

Increased bilirubin, grades 3-4 (21%) 

Delirium (21%) 

Bacterial infection (19%) 

Prolonged neutropenia, Day 56 (17%) 

Infection, unspecified pathogen, grades 3-4 (16%) 

Hypofibrinogenemia with grades 3-4 CRS (16%) 

Abdominal pain (16%) 

Constipation (18%) 

Viral infection, grades 3-4 (18%) 

Hypoxia, grades 3-4 (18%) 

Pain (18%) 

Prolonged neutropenia, Day 56 (17%) 

Infection, unspecified pathogen, grades 3-4 (16%) 

Pain in extremity (16%) 

Pyrexia, grades 3-4 (15%) 

Myalgia (15%) 

Fungal infection (13%) 

Pulmonary edema (16%) 

Rash (16%) 

Decreased appetite, grades 3-4 (15%) 

Anxiety (13%) 

Increased INR (13%) 

Prolonged thrombocytopenia, Day 56 (12%) 

Arthralgia (12%) 

Tachypnea (12%) 

Dyspnea, grades 3-4 (12%) 

Bacterial infection, grades 3-4 (13%) 

Acute kidney injury, grades 3-4 (13%) 

1-10% (Pediatric & Young Adults with ALL) 

Sleep disorders (10%) 

Face edema (10%) 

Back pain (10%) 

Pleural effusion (10%) 

Nasal congestion (10%) 

Histiocytosis lymphocytic hemophagocytosis (7%) 

Coagulopathy (6%) 

Blood creatinine increased (7%) 

Pulmonary edema, grades 3-4 (10%) 

Peripheral edema, grades 3-4 (10%) 

Chills (10%) 

Fluid overload (10%) 

Encephalopathy, grades 3-4 (10%) 

Fungal infection, grades 3-4 (7%) 

Blood and lymphatic system disorders: DIC (9%) 

aPTT prolonged (6%) 

Cardiac disorders: Cardiac arrest (4%), cardiac failure (7%) 

Metabolism and nutrition disorders: Tumor lysis syndrome (6%) 

Vascular disorders: Capillary leak syndrome (3%) 

Respiratory, thoracic, and mediastinal disorders:  

Respiratory distress (6%), respiratory failure (6%), acute RDS (4%) 

General disorders and administration site conditions: Multiple organ dysfunction syndrome (3%) 

Immune system disorders: GVHD (1%) 

Nervous System: Intracranial hemorrhage (1%), seizure (3%) 

Gastrointestinal disorders: Abdominal compartment syndrome (1%) 

1-10% (Adults with DLBCL) 

Arthralgia (10%) 

Hypotension, grades 3-4 (8%) 

Acute kidney injury, grades 3-4 (6%) 

Dyspnea, grades 3-4 (6%) 

Hypogammaglobulinemia, grades 3-4 (4%) 

Appetite decreased, grades 3-4 (4%) 

Fatigue, grades 3-4 (7%) 

Pyrexia, grades 3-4 (6%) 

Weight decreased, grades 3-4 (3%) 

Nausea, grades 3-4 (1%) 

Constipation, grades 3-4 (1%) 

Edema, grades 3-4 (2%) 

Diarrhea, grades 3-4 (1%) 

Tachycardia, grades 3-4 (3%) 

Pain, grades 3-4 (3%) 

Dizziness, grades 3-4 (1%) 

>10% (Adults with DLBCL) 

Lymphopenia, grades 3-4 (97%) 

Neutropenia, grades 3-4 (81%) 

Pyrexia (34%) 

Hypotension (26%) 

Infection, unspecified pathogen grades 3-4 (25%) 

Thrombocytopenia, grades 3-4 (54%) 

Leukopenia, grades 3-4 (77%) 

Cytokine release syndrome (74%) 

Anemia, grades 3-4 (58%) 

infection, unspecified pathogen (42%) 

Hypophosphatemia (24%) 

Diarrhea (31%) 

Nausea (27%) 

Fatigue (26%) 

Headache (21%) 

Cough (19%) 

Dyspnea (18%) 

Acute kidney injury (17%) 

Constipation (16%) 

Hypogammaglobulinemia (14%) 

Tachycardia (13%) 

Chills (13%) 

Dizziness (11%) 

Encephalopathy, grades 3 & 4 (11%) 

Febrile neutropenia, grades 3-4 (17%) 

Cytokine release syndrome, grades 3-4 (23%) 

Edema (23%) 

Pain (15%) 

Encephalopathy (16%) 

Decreased appetite (12%) 

Hypokalemia (12%) 

Hyponatremia (11% 

Decreased weight (11%) 

Black Box Warning

Black Box Warning 

The black box warning for tisagenlecleucel refers to the possibility of neurological toxicity including CRS. When the modified T-cells get activated and produce a huge number of cytokines, a condition known as “cytokine release syndrome” may develop.

In extreme situations, organ failure and shock may result from the excessive cytokine release. After tisagenlecleucel therapy, neurological toxicities such disorientation, seizures, and delirium are also possible. 

The black box warning highlights the necessity for healthcare professionals to regularly monitor patients for CNS toxicities and CRS side effects, and to have the right management strategies in place. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Those who are sensitive to any of the tisagenlecleucel’s ingredients. 
• Individuals with inflammatory or active infections, since these conditions may increase one’s risk of cytokine release syndrome (CRS) and other possible adverse effects. 

Caution: 

• tisagenlecleucel shouldn’t be taken during pregnancy unless the possible benefits outweigh the dangers since it might damage a growing foetus. 
• Breastfeeding is not advised for at least 4 weeks after receiving tisagenlecleucel medication since it is uncertain whether the drug is excreted in breast milk. 
• Adverse effects may be more likely if a patient has already received other CAR T-cell treatments. 
• Individuals may be more vulnerable to neurological toxicities if they already have neurological diseases or CNS metastases. 
• Individuals who have previously received chemotherapy or radiation therapy may be more susceptible to neurological toxicities or severe cytokine release syndrome (CRS). 
• CRS risk may be higher in patients with a history of immunosuppressive treatment 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: NA 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology:  

tisagenlecleucel’s pharmacology is based on its capacity to alter a patient’s own T-cells so that they can detect and target cancer cells. 

The modified CAR T-cells can continue to proliferate and assault cancer cells for a considerable amount of time despite the drug’s short (16 hours) half-life. 

When CAR T-cells are activated, cytokines may be released, which may have adverse consequences including fever, flu-like symptoms, and low blood pressure. 

Pharmacodynamics 

tisagenlecleucel’s pharmacodynamics is based on its capacity to bind to CD19, a protein expressed on the surface of B-cells and stimulate the transformed T-cells to detect and destroy cancer cells. 

The quantity of modified T-cells infused, the medication dose, and the unique immunological response of the patient can all affect the pharmacodynamics of tisagenlecleucel. Although the modified T-cells continue to assault cancer cells and other cells that express CD19, patients who take tisagenlecleucel may also undergo a period of immune system suppression after therapy. 

Pharmacokinetics 

Absorption   

tisagenlecleucel is absorbed quickly and completely into the circulation since it is given as an intravenous infusion.  

Distribution   

tisagenlecleucel cells are injected and dispersed all throughout body, where they may identify and kill cancer cells that exhibit CD19. The altered T-cells can assault cancerous cells in the brain by overcoming the blood-brain barrier. 

Metabolism   

tisagenlecleucel is predominantly metabolized by the T cells that received it. Long-lasting effectiveness may result from the modified T-cells’ ability to reproduce and target cancer cells long after injection. 

Elimination and excretion   

tisagenlecleucel is expelled from the body as a result of regular cellular turnover. Although the transformed T-cells have a half-life of just around 16 hours, they can continue to proliferate and assault cancer cells for a long time after that. 

Adminstartion

Administration:  

Cellular treatment called tisaglecleucel is given as a single intravenous infusion. To reduce the danger of adverse effects, the dosage of tisagenlecleucel is a complicated procedure that needs careful monitoring and supervision.

In order to be sure that the modified T-cells are successfully destroying cancer cells and to handle any potential adverse effects that may manifest, patients who get tisagenlecleucel should be continuously watched by medical professionals for several weeks to months following the infusion. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tisagenlecleucel 

Why do we use tisagenlecleucel? 

tisagenlecleucel is an immunotherapy drug used to treat a particular kind of acute lymphoblastic leukaemia in patients who are up to 25 years old. 

tisagenlecleucel is used when previous therapies have failed.