Drugs List

Therapeutic Indications

Uses

Severe combined immunodeficiency due to adenosine deaminase deficiency

Treatment of patients with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) with no suitable human leukocyte antigen related stem cell donor.

Administration

Autologous CD34+ cells transduced to express human adenosine deaminase is administered by intravenous infusion.

The treatment should be prepared according to the manufacturer's instructions.

Contraindications

History of gene therapy
Patients over 65 years
Breastfeeding
Hepatitis B
Hepatitis C
Leukaemia
Myelodysplastic syndrome
Positive HIV status
Pregnancy

Precautions and Warnings

Children aged 6 to 18 years
Children under 6 months

Sodium content of formulation may be significant
Premedication with antihistamine recommended
For autologous use only
Treatment to be administered by or under supervision of specialist
Autoimmune disorders can occur many months after initiation of treatment
Monitor full blood count regularly
Monitor patient for catheter-related adverse events
Monitor patient for signs of serious infection
Risk of developing opportunistic infections
Female:Barrier contraception required during & for 6 months after treatment
Advise patient to avoid donating blood, organs, tissues or cells

Confirm the patient's identity match the unique patient information prior to infusion.

Patients previously positive with hepatitis C will require three sequential negative test results over a period of 4 weeks, the final test will need to be conducted within three days prior to cell harvest. Nucleic acid test results with a limit of quantification of below 15 international units/ml are required.

Due to a potential risk of leukaemia transformation, patients require a complete blood count with differential, biochemistry and thyroid stimulating hormone annually for the first eleven years and then at thirteen and fifteen years following treatment.

Possibility of treatment failure with older patients should be considered due to lower availability of CD34+ cells. Treatment should be reserved only when all other alternative treatment options have been considered.

Avoid treatment if a positive test for any infectious agents listed in the EU Cell and Tissue Directive prior to bone marrow harvest.

Pregnancy and Lactation

Pregnancy

Autologous CD34+ cells transduced to express human adenosine deaminase is contraindicated during pregnancy.

The manufacturer states that limited data on exposed pregnancies are available and reproductive or developmental toxicity studies were not performed.

Lactation

Autologous CD34+ cells transduced to express human adenosine deaminase is contraindicated during breastfeeding.

The manufacturer states that it is unknown whether autologous CD34+ cells transduced to express human adenosine deaminase are excreted in human milk. At the time of writing there are no studies on the effect of breast-fed infants following the administration of the treatment to their mothers.

Side Effects

Allergic dermatitis
Anaemia
Anti-neutrophil cytoplasmic antibodies (ANCA)
Asthma
Autoimmune disorders
Autoimmune hepatitis
Eczema
Guillain-Barre syndrome
Hypertension
Hypothyroidism
Increase in antinuclear antibodies (ANA)
Increases in hepatic enzymes
Neutropenia
Pyrexia
Rhinitis
Smooth muscle antibody positive

Presentation

Infusion of autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes human adenosine deaminase (ADA) cDNA sequence.

Drugs List

Therapeutic Indications

Uses

Severe combined immunodeficiency due to adenosine deaminase deficiency

Treatment of patients with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) with no suitable human leukocyte antigen related stem cell donor.

Dosage

Pre-treatment
Busulfan 0.5 mg/kg every 6 hours intravenously for two consecutive days starting three days before treatment.

Measure busulfan plasma levels after the first dose of each day. Reduce dose of busulfan if AUC exceeds 4000 nanograms/ml/hour.

Treatment
2 to 20 million CD34+ cells/kg as a single dose.

If the product contains less than 2 million CD34+ cell/kg, a decision needs to be made on whether or not to proceed with the treatment due to previous treatment failures with doses below 2 million CD34+ cell/kg.

Additional Dosage Information

Administration

Autologous CD34+ cells transduced to express human adenosine deaminase is administered by intravenous infusion.

The treatment should be prepared according to the manufacturer's instructions.

Contraindications

History of gene therapy
Patients over 65 years
Breastfeeding
Hepatitis B
Hepatitis C
Leukaemia
Myelodysplastic syndrome
Positive HIV status
Pregnancy

Precautions and Warnings

Children aged 6 to 18 years
Children under 6 months

Sodium content of formulation may be significant
Premedication with antihistamine recommended
For autologous use only
Treatment to be administered by or under supervision of specialist
Autoimmune disorders can occur many months after initiation of treatment
Monitor full blood count regularly
Monitor patient for catheter-related adverse events
Monitor patient for signs of serious infection
Risk of developing opportunistic infections
Female:Barrier contraception required during & for 6 months after treatment
Advise patient to avoid donating blood, organs, tissues or cells

Confirm the patient's identity match the unique patient information prior to infusion.

Patients previously positive with hepatitis C will require three sequential negative test results over a period of 4 weeks, the final test will need to be conducted within three days prior to cell harvest. Nucleic acid test results with a limit of quantification of below 15 international units/ml are required.

Due to a potential risk of leukaemia transformation, patients require a complete blood count with differential, biochemistry and thyroid stimulating hormone annually for the first eleven years and then at thirteen and fifteen years following treatment.

Possibility of treatment failure with older patients should be considered due to lower availability of CD34+ cells. Treatment should be reserved only when all other alternative treatment options have been considered.

Avoid treatment if a positive test for any infectious agents listed in the EU Cell and Tissue Directive prior to bone marrow harvest.

Pregnancy and Lactation

Pregnancy

Autologous CD34+ cells transduced to express human adenosine deaminase is contraindicated during pregnancy.

The manufacturer states that limited data on exposed pregnancies are available and reproductive or developmental toxicity studies were not performed.

Lactation

Autologous CD34+ cells transduced to express human adenosine deaminase is contraindicated during breastfeeding.

The manufacturer states that it is unknown whether autologous CD34+ cells transduced to express human adenosine deaminase are excreted in human milk. At the time of writing there are no studies on the effect of breast-fed infants following the administration of the treatment to their mothers.

Side Effects

Allergic dermatitis
Anaemia
Anti-neutrophil cytoplasmic antibodies (ANCA)
Asthma
Autoimmune disorders
Autoimmune hepatitis
Eczema
Guillain-Barre syndrome
Hypertension
Hypothyroidism
Increase in antinuclear antibodies (ANA)
Increases in hepatic enzymes
Neutropenia
Pyrexia
Rhinitis
Smooth muscle antibody positive

Further Information

Last Full Review Date: October 2021

Reference Sources

Summary of product characteristics: Strimvelis 1-10 million cells/ml dispersion for infusion. Orchard Therapeutics (Europe) Ltd. Revised January 2021.