CAR-T Cell Therapy

Question 1

Function

Answer 1

Genetically engineered T-cells that produces an artificial T-receptor with a new ability to target a specific protein

Question 2

For safety

Answer 2

CAR-T cells are engineered to be specific to an antigen over-expressed on a tumour e.g. CD19

Question 3

Lymphodepletion

Answer 3

Use of high dose chemotherapy to condition the microenvironment and reduces tumour load
Improves CAR-T expansion and persistence, increasing efficacy and long-term survival of CAR-T
Decreases lymphocytes to make space for CAR-T cells

Question 4

Lymphodepletion medicines

Answer 4

Combination of Fludarabine and Cyclophosphamide

Question 5

Prophylaxis for Tumour Lysis Syndrome

Answer 5

Allopurinol 300mg OD + oral hydration
28 days commencing on first day of LD
Prevents uric acid build up due to chemotherapy = kills cancer cells releasing uric acid

Rasburicase 3mg IV + IV hydration
G6PD status need to check as it is contraindicated in patients with G6PD deficiency
Prevents acute renal failure = controls uric acid build up

Question 6

Prophylaxis for N+V

Answer 6

Ondansetron 8mg orally BD +
Domperidone or metoclopramide 10mg orally TDS

Question 7

Prevention of urothelial toxicity from Cyclophosphamide

Answer 7

Cyclophosphamide irritates bladder lining causing bleeding = Mesna given to protect the bladder and reduce the risk of haemorrhagic cystitis

Mesna IV 20% of Cyclophosphamide or Mesna orally 40% of Cyclophosphamide

Question 8

Anti-seizure prophylaxis

Answer 8

Levetiracetam 500mg - 750mg orally BD

Question 9

Menstruation suppression

Answer 9

Norethisterone 5mg orally TDS for pre-menopausal females at risk of thrombocytopenia

Buserilin 150mcg/dose nasal spray - alternative to Norethisterone for breakthrough bleeding

Question 10

Pre-medications / rescue medicines for infusion related reactions (IRRs)

Answer 10

Chlorphenamine 10mg IV
Paracetamol 1g orally
Pethidine 12.5mg - 25mg IV

Corticosteroids - not given as it decreases the efficacy of CAR-T therapy

Question 11

Rescue medicines for acute toxicities

Answer 11

Tocilizumab 8mg/kg IV

Question 12

Antiviral prophylaxis

Answer 12

Aciclovir 400mg orally BD
or
Valaclicovir 500mg orally BD

Question 13

Antipneumocystis prophylaxis

Answer 13

Co-trimoxazole 960mg orally three times a week

Pentamidine inhalation 300mg once a month or Dapsone orally 100mg OD or Atovaquone 750mg orally BD - Co-trimoxazole allergy or cytopenia

Question 14

Systemic anti-fungal prophylaxis

Answer 14

Fluconazole 200mg orally daily

Posaconazole 300mg orally BD

Question 15

Antibacteria prophylaxis

Answer 15

Ciprofloxacin 250 orally BD - may be considered in case of prolonged neutropenia

Question 16

Hep B virus prophylaxis or patients with history of HepB infection

Answer 16

Entecavir 500mg orally OD or
Teneforvir disoproxil 25mg orally

Question 17

Cytokine Release Syndrome (CRS)

Answer 17

Life threatening condition caused by rapid release of cytokines into the blood from activated CAR-T cells
Happens within the first 10 days of treatment

Question 18

Symptoms of CRS

Answer 18

Ranges from mild flu-like symptoms to severe reactions including high fever, low blood pressure, hypoxia and organ dysfunction

Question 19

CRS treatment: Grade 1

Answer 19

Monitor vital signs q4h
Treat as per neutropenic sepsis guidelines - paracetamol, IV fluids, broad spectrum abx
Consider Tocilizumab 8mg/kg

Question 20

CRS treatment: Grade 2

Answer 20

Monitor vital signs hourly
Treat as per neutropenic sepsis guidelines - paracetamol. IV fluids, broad spectrum abx
Administer Tocilizumab 8mg/kg
Consider IV Dexamethasone 10mg BD - QDS
Administer Oxygen as required

Question 21

CRS treatment: Grade 3

Answer 21

Transfer to ICU
Treat as per neutropenic guidelines - paracetamol, IV fluids, broad spectrum abx
Continuous cardiac monitoring - consider ECHO
Administer vasopressors - Epinephrine, Norephinephrine, Dopamine
Administer Oxygen as required
Administer Tocilizumab 8mg/kg
Administer IV Dexamethasone 10mg BD - QDS
Consider IV Methyprednisolone - if refractory

Question 22

CRS treatment: Grade 4

Answer 22

Transfer to ICU
Treat as per neutropenic guidelines - paracetamol, IV fluids, broad spectrum abx
Continuous cardiac monitoring - consider ECHO
Administer vasopressors - Epinephrine, Norephinephrine, Dopamine
Administer Oxygen as required
Administer Tocilizumab 8mg/kg
Administer IV Dexamethasone 10mg BD - QDS or high dose IVE Methylprednisolone 1g

Question 23

ICANS

Answer 23

Neurotoxicity after CAR-T cells therapy

Question 24

ICANS symptoms

Answer 24

Altered level of consciousness
Cognitive skills impairment
Motor weakness
Seizures
Cerebral oedema

Question 25

ICANS treatment: Grade 1

Answer 25

Close monitoring Neurological examination TDS ICE score Consider seizure prophylaxis Consider Tocilizumab if concurrent CRS

Question 26

ICANS treatment: Grade 2

Answer 26

Regular neurological observations TDS ICE score Administer IV Dexamethasone 10mg BD - QDS Consider Tocilizumab if concurrent CRS

Question 27

ICANS treatment: Grade 3

Answer 27

Transfer to ICU / Neuro ICU Regular neurological observations TDS ICE score Repeat neuroimaging and EEG Administer antiepileptics Administer IV Dexamethasone 10mg QDS Consider IV Methylprednisolone - if refractory Administer Tocilizumab if concurrent CRS

Question 28

ICANS treatment: Grade 4

Answer 28

Transfer to ICU / Neuro ICU Regular neurological observations TDS ICE score Repeat neuroimaging and EEG Administer antiepileptics Administer IV Dexamethasone 10mg QDS or high dose IV Methylprednisolone 1g Administer Tocilizumab if concurrent CRS

Question 29

Neutropenic Sepsis | What to give

Answer 29

Paracetamol Broad spectrum abx - Tazocin, Gentamicin or Amikacin

Question 30

Invasive Aspergillosis

Answer 30

Broad spectrum azoles - Isavuconazole and Voriconazole Second line - Caspifungin or Microfungin Ampothericin B liposomal - low risk patients / prophylaxis