Screening Investigations
Patients referred for commercial CAR-T therapy must have disease that meets the TGA approved product specifications. In most cases, this will require a tissue or bone marrow biopsy confirming CD19-positive disease following their most recent line of therapy, and/or confirmation of disease on imaging (PET or CT).
Additional investigations may be required at the time of screening or CAR-T therapy including:
- Bone marrow aspirate and trephine (including cytogenetics, BCR-ABL and MRD studies for B-ALL)
- Lumbar puncture and/or MRI brain if prior evidence of CNS disease or neurological symptoms
- Recent echocardiogram or MUGA study
- FBC, EUC, CMP, LFTs, LDH, immunoglobulins, SPEP
- Viral serology and molecular testing (HBV, HCV, HIV, syphilis, HTLV)
- Negative serum pregnancy test in females of child-bearing age
- 24 hour urine creatinine clearance estimation
- Lung function studies (if history of significant respiratory disease)
- ECG, CXR, OPG and dental review
While all blood work-up and bone marrow studies should be undertaken at the CAR-T infusion centre, it may be possible to arrange some of the other investigations elsewhere (e.g. cardiac assessment, pulmonary assessment, renal assessment, scans).
CAR-T Therapy timeline
Following referral, review and screening of the patient for eligibility will be performed through the Alfred CAR-T clinic.
Once approved and consented for CAR-T therapy, patients will undergo leukapharesis (without mobilisation) as an outpatient in our day oncology centre. Patients must have observed the required wash out period for recent cancer treatments.
Collected autologous T cells will be sent fresh or cryopreserved to the site of manufacture where they undergo genetic alteration using viral vectors, as well as microbial contamination testing.
Once the manufactured CAR-T product has been returned to the Alfred, patients will be admitted for lymphodepleting chemotherapy involving intravenous Fludarabine and Cyclophosphamide over a 3 to 4 day period, followed by CAR-T cell infusion.
Patients will be monitored as an inpatient for 10 to 14 days (possibly longer if experiencing side effects of treatment). Following discharge, they will be required to remain within 1 hour of the Alfred under the supervision of a full time carer for at least 28 days post CAR-T cell infusion. During this time they will be regularly reviewed by our CAR-T team in person in our day oncology centre. Following this initial 28 day period, if well, patients will be allowed to return to their normal residence and will continue to receive follow-up review either in person or through telehealth. Patients will undergo disease re-assessment at 1, 3, 6 and 12 months post treatment.
The process from patient screening to CAR-T cell infusion can take anywhere from 4 to 8 weeks. For patients with aggressive disease kinetics or bulky disease at time of screening, bridging therapy may be required and is able to be delivered following leukapharesis and prior to CAR-T cell infusion. If bridging therapy is required, it is the expectation that this be administered by the referring centre following discussion regarding timing and regimens with the Alfred CAR-T team.
Source: Novartis