Aucatzyl must be administered in a qualified treatment centre by a physician with experience in the treatment of haematological malignancies and trained for administration and management of patients treated with the medicinal product.
In the event of cytokine release syndrome (CRS), at least one dose of tocilizumab, and emergency equipment, must be available prior to infusion. 4). , siltuximab) to treat CRS instead of tocilizumab must be available prior to infusion.
4). The target dose is 410 × 106 CD19 CAR-positive viable T cells (range: 308-513 × 106 CAR-positive viable T cells) supplied in 3 or more infusion bags. The treatment regimen consists of a split dose to be administered on day 1 and day 10 (± 2 days).
The dose regimen will be determined by the tumour burden assessed by bone marrow (BM) blast percentage from a sample obtained within 7 days prior to the start of lymphodepletion (Figure 1). The RfIC and Dose Schedule Planner (Annex IIIA), located inside the lid of the cryoshipper, must be followed for the actual cell counts and volumes to be infused and to guide the appropriate dose regimen.
Bone marrow assessment A BM assessment must be available from a biopsy and/or aspirate sample obtained within 7 days prior to the commencement of the lymphodepleting chemotherapy.
The BM assessment will be used to determine the Aucatzyl dose regimen:
High Tumour Burden Regimen if blast percentage is > 20% or Low Tumour Burden Regimen if blast percentage is ≤ 20% (see Figure 1). If BM assessment results are inconclusive, the biopsy or aspirate must be repeated (but only once). A repeat biopsy or aspirate should only be taken prior to lymphodepleting chemotherapy.
, administration of the 10 × 106 dose on day 1 per Figure 1).
Figure 1:
Aucatzyl tumour burden adjusted split dose regimen High tumour burden dose regimen (Bone marrow blast > 20% or inconclusive) Day 1 Day 10 (± 2 days) 10 × 106 dose administered via syringe* 100 × 106 dose administered via bag infusion+ and 300 × 106 dose administered via bag infusion+ 4 Low tumour burden dose regimen (Bone marrow blast ≤ 20%) Day 1 Day 10 (± 2 days) 100 × 106 dose administered via bag infusion+ 10 × 106 dose administered via syringe* and 300 × 106 dose administered via bag infusion+ *The exact volume to be administered via syringe is indicated in the RfIC.
The 10 × 106 CD19 CAR-positive viable T cell bag configuration contains an overfill, and therefore it is important to withdraw only the volume specified. +The 100 × 106 and 300 × 106 doses will be suspended in one or more infusion bags with no overfill.
1). Pretreatment (lymphodepleting chemotherapy) The lymphodepleting chemotherapy regimen must be administered before infusion of Aucatzyl: fludarabine (FLU) 30 mg/m2/day intravenously and cyclophosphamide (CY) 500 mg/m2/day intravenously on days -6 and -5, followed by fludarabine on days -4 and -3 (total dose: FLU 120 mg/m2; CY 1 000 mg/m2).
For dose modifications of cyclophosphamide and fludarabine, see corresponding Summaries of Product Characteristics of cyclophosphamide and fludarabine. Retreatment with lymphodepleting chemotherapy, in patients who could not receive the Aucatzyl dose on day 1 as planned, could be considered if there is an Aucatzyl dose delay of more than 10 days.
Lymphodepleting chemotherapy should not be repeated after the first dose of Aucatzyl is administered. Aucatzyl is infused 3 days (± 1 day) after completion of lymphodepleting chemotherapy (day 1), allowing a minimum 48-hour washout.
4). A delay to the second split dose may be required to manage toxicities. 5 to 25 mg intravenously or orally (or equivalent medicinal products) approximately 30 minutes prior to Aucatzyl infusion. Prophylactic use of systemic corticosteroids is not recommended .
Reasons to delay treatment Delay Aucatzyl treatment if there are unresolved serious adverse reactions from preceding chemotherapies, if the patient is experiencing severe intercurrent infection, or has active graft-versus-host disease.
If the patient requires supplementary oxygen, Aucatzyl should only be infused, if considered appropriate, based on the treating physician’s benefit / risk assessment. Reasons to delay the second split dose 5 Dose delays or discontinuation of treatment may be required after the first split dose to manage adverse reactions as described in Table 1.
Table 1:
Dose delay or discontinuation - guidance intended to reduce the risk of adverse reactions Adverse reaction Gradea Actions Second split dose Day 10 (± 2 days) Cytokine release syndrome (CRS) following the first split dose Grade 2 Consider postponing Aucatzyl infusion up to day 21 to allow for the CRS to resolve to grade 1 or less.
If the CRS persist beyond day 21, do not administer the second dose. Grade ≥ 3 Discontinue treatment. 4) Grade 1 Consider postponing Aucatzyl infusion up to day 21 to allow for the ICANS to completely resolve. If the ICANS persist beyond day 21, do not administer the […]