by
Kara Wacker, MBA, RAC, Strategic Planning Adminstrator
Foundation for the Accreditation of Cellular Therapy
Omaha, NE USA
As part of FACT accreditation, cellular therapy organizations voluntarily comply with quality improvement-related standards intended to improve patient care as the field progresses and more is learned. FACT committee rosters are full of volunteer experts who experience the same advancements as accredited organizations, and they work with their peers to answer the inevitable ambiguities that come with change.
Representatives on the FACT Immune Effector Cell Task Force and FACT Clinical Outcomes Improvement Committee provide their insight related to common questions FACT has received regarding immune effector cell therapy accreditation and evaluation of patient survival. Two recent questions relate to bispecific T cell engagers (BiTEs) and high-risk transplant patients.
A Bit About BiTEs and Their Relationship to FACT Accreditation
Utilizing a patient’s immune system to combat cancer is a hot topic in research and in translational medicine, with several therapies now commercially available for use. In 2017, FACT published standards and implemented an accreditation program for immune effector cells (IECs), defined as, “A cell that has differentiated into a form capable of modulating or effecting a specific immune response.”1 This definition includes, but is not limited to, cell-based therapies such as chimeric antigen receptor (CAR) T cells, tumor infiltrating lymphocytes (TILs), T cell receptor (TCR)-modified T cells, therapeutic vaccines, and NK- or B-cell based therapies. Activities related to IECs that are performed at FACT-accredited cellular therapy programs must comply with FACT Standards.
But what about BiTEs? Bispecific T cell engagers are emerging as an efficacious therapy that leads T cells to fight tumor cells.2 FACT-accredited programs are increasingly using them in their own programs but also see oncologists in other institutional departments or in other practices prescribing them. They have an immunological mechanism of action, but they are antibodies rather than a cell-based therapy. Therefore, they are not specifically eligible for FACT accreditation or required to be administered by an accredited program.
When handled on a FACT-accredited unit, BiTEs should be treated like any other drug or antibody: utilizing standard operating procedures, personnel trained to administer them and recognize toxicities, confirmation of correct patient and drug, etc. BiTEs do have toxicities similar to CAR-T cells, such as cytokine release syndrome. When administered by medical staff not affiliated with a FACT-accredited IEC or transplant team, it may be useful for the IEC or transplant team to assist as needed with toxicity management, but this is not required.
Because BiTEs have similar toxicities, experience with them may prepare nurses and other staff with management of CAR-T patients in the future. Utilizing BiTEs experience may assist programs preparing to onboard and seek accreditation for IECs.
1 Foundation for the Accreditation of Cellular Therapy and Joint Accreditation Committee – ISCT and EBMT. FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration (Eighth Edition); 2021.
2 Tian, Z., Liu, M., Zhang, Y. et al. Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. J Hematol Oncol 14, 75 (2021). https://doi.org/10.1186/s13045-021-01084-4.
Public Reporting of Survival and its Impact on Patient Volumes
Since 2015, FACT Standards have required transplant programs to evaluate one-year survival in comparison to national or international data and submit a corrective action plan (CAP) when survival does not meet the expected range. Allogeneic transplant programs in the U.S. must utilize the annual CIBMTR Transplant Center-Specific Analysis (CSA) report as its comparative data. The FACT Clinical Outcomes Improvement Committee evaluates CAPs against defined guidelines using an established policy. Updates to this policy were announced in 2022.
Sharma et. al. recently published an article titled, Impact of Public Reporting of Center-Specific Survival Analysis Scores on Patient Volumes at Hematopoietic Cell Transplant Centers.1 The authors evaluated the impact of public reporting of survival on allogeneic transplant volumes. Data show that public reporting is associated with changes in volume, including lower volume at programs that do not meet expected one-year survival as reported in the CSA. There is a plethora of reasons for why this may be the case, and some are briefly listed in the article.
As part of FACT’s process for evaluating CAPs intended to improve one-year survival, the FACT Outcomes Committee generally does not accept refusal to transplant high-risk patients as a blanket corrective action.2 The committee is mindful of how its reviews should not impact patient access to transplant. Furthermore, refusal to treat high-risk patients may not improve outcomes: The CSA uses risk-adjusted methodology, meaning that the expected range of one-year survival already accounts for the level of risk. Attempts to improve outcomes simply by refusing to treat high-risk patients will be ineffective. The program’s level of risk would simply be lower, causing a higher expected range of one-year survival in subsequent reports.
To improve survival, the committee encourages transplant programs to focus on the cause of death. Perhaps preparative regimens are too aggressive or not aggressive enough, certain comorbidities need to be managed, socioeconomic barriers require greater social support to ensure medication compliance, or patients are being referred to the program too late. Addressing these root causes may improve survival while giving patients a treatment option.
Finally, research involving high-risk patients advances the field. If transplant programs were to only transplant the easy cases, no improvements would be made. This is a research-oriented field, and the greatest challenges will improve transplant and make it an option for more patients, not less.
1 Sharma et. al. Impact of Public Reporting of Center-Specific Survival Analysis Scores on Patient Volumes at Hematopoietic Cell Transplant Centers. Transplantation and Cellular Therapy, 29, 8 (2023). https://doi.org/10.1016/j.jtct.2023.05.013.
2 LeMaistre et. al. Integration of Publicly Reported Center Outcomes into Standards and Accreditation: The FACT Model. Transplantation and Cellular Therapy, 25, 11 (2019).
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