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I. Yakoub-Agha et al.
accredited allogeneic HCT program, where established facilities, staffing and expertise can support most aspects of the CAR T-cell pathway. Regardless, the logistical impact of IEC administration within a HCT program has to be carefully planned; an implementation plan aimed at meeting all accreditation and other regulatory require- ments, while engaging all professionals, services and infra- structure, is essential. Before starting, an assessment of the number of eligible patients and likely resource require- ments will usually have to be reviewed by the competent authorities and other regulators, as well as by funding bodies. As mandated by the EMA, the pharmaceutical manufacturers also have their own requirements and rou- tinely inspect facilities before a CAR T-cell program is commenced.
The EBMT and JACIE expect that most CAR T-cell activity in Europe will be delivered by experienced allo- geneic HCT centers and, ultimately, as the accreditation cycles of centers roll through to the 7th edition of the stan- dards, the IEC standards will be covered at routine allo- geneic HCT re-accreditation inspections. For the minority of centers that undertake CAR T-cell therapy outside of an accredited allogeneic HCT program, there are a number of options. Given that CAR T-cell therapy is presently used predominantly in B-cell non-Hodgkin lymphoma, there is the possibility of achieving the IEC standards as part of the accreditation covering autologous HCT, given that referral for autologous HCT is common in lymphoma practice. The same considerations could also apply to myeloma specialists working outside of allogeneic HCT programs, as IEC accreditation standards could be aligned to autologous HCT activity or referral routes routinely established in every myeloma service.
In the event of CAR T-cell or related therapies becoming more broadly applicable to non-hematologic cancers and
therefore potentially outside mainstream transplant prac- tice, there are a number of possible routes. First, there may be referral to an accredited HCT program, where shared care arrangements can be easily accommodated within the quality management systems and service level agree- ments. This is a model that already applies to occasional HCT in solid tumors, such as germ cell tumors, where patients are referred back at a mutually agreed, often early, stage after transplantation for ongoing care by the refer- ring medical or clinical oncologists.
An alternative strategy would be to undertake inde- pendent IEC accreditation specifically for CAR T-cell and other IEC therapies. This would have to be an individual decision, based on the number of patients undergoing therapy in a given center, as to whether the establishment of a functional quality system and other generic measures were justified just for CAR T-cell or other IEC therapy. The EBMT and JACIE are currently evaluating the demand and feasibility of this approach, which has been adopted by FACT.
Currently, the general recommendation from the EBMT and JACIE is that CAR T cells and other IEC are best deliv- ered within the framework of an accredited HCT program, whether allogeneic or autologous, with shared care poli- cies and service level agreements incorporated into the quality systems of the HCT program. Importantly, JACIE also provides a robust method to ensure that programs meet the quality and other requirements for mandatory long-term data submission to the EBMT registry, as well as potential benchmarking of survival outcomes.
Acknowledgments
The authors would like to thank all respondents to the interna- tional survey on the management of patients receiving CAR T-cell therapy.
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