1.
ASCT vs CART for Patients with Relapsed LBCL in PR: Role of TMTV
Strati, P., Pasvolsky, O., Feng, L., Xu, G., Tewari, S., Varghese, J., Ow, K., Santiago, M. S., Al Zaki, A., Jallouk, A., et al
Blood advances. 2023
2.
Paving the Road for CAR-Ts: ASTCT 80/20 Task Force consensus on challenges and solutions to improving efficiency of clinical center certification and maintenance of operations for commercially approved immune effector cell therapies
Nikiforow, S., Frigault, M. J., Frey, N. V., Gardner, R. A., Komanduri, K. V., Perales, M. A., Kebriaei, P., Warkentin, P. I., Pasquini, M., Aho, J. L., et al
Transplantation and cellular therapy. 2023
Abstract
As the number and type of regulatory authority-approved cellular therapies grow, clinical treatment centers face a heavy burden of duplicative documentation around initial qualification, ongoing auditing, and reporting-with overlapping requirements from each manufacturer to ensure safe use of their specific product, which in the United States are stipulated under individual Food and Drug Administration (FDA) Biologic License Applications (BLA). The American Society for Transplantation and Cellular Therapy (ASTCT) convened the 80/20 Taskforce to consider challenges and potential solutions to these issues. The taskforce proposed that 80% of manufacturers' requirements for onboarding and ongoing operations of commercially available products could be standardized and streamlined. Taskforce members interviewed dozens of stakeholders, including clinicians at large academic medical centers already utilizing commercial and investigational immune effector cell (IEC) products, regulators, members of accrediting bodies and professional cellular therapy societies, and manufacturers of IEC therapies for oncologic indications. In November 2021, the taskforce organized and led virtual discussions in a public forum and at a private ASTCT 80/20 workshop at the online AcCELLerate Forum, a cellular-therapy stakeholders' meeting organized by the ASTCT, the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR). At the workshop, approximately 60 stakeholders worked to identify and prioritize common challenges in onboarding and maintenance of operations at clinical sites for commercial FDA-approved and future IEC therapies and ways to streamline the process. It was agreed that standardization would improve efficiency of onboarding, allowing more cost-effective, sustainable growth of approved IEC therapies at treatment centers, and facilitate wider access while maintaining safety and clinical success. This early but extensive survey of stakeholders resulted in five overarching suggestions for both established and emerging treatment centers: 1. Eliminate duplication in accreditation and auditing of clinical sites; 2. Define expectations for education and management of CAR-T cell therapy toxicities to potentially replace product-specific REMS programs; 3. Streamline current REMS education, testing and data reporting; 4. Standardize IT platforms supporting enrollment, clinical site-to-manufacturer communication, and logistics of maintaining chain of identity/chain of custody across multiple transportation steps; 5. Encourage use of universal nomenclature by cell therapy manufacturers. Future discussions need to engage a broader range of stakeholders including administrators, pharmacists, nurses, data coordinators, surgeons, pathologists, and those developing promising cellular therapies for solid tumors, as well as teams from smaller academic or community cancer center settings. Continued collaboration with stakeholders outside of clinical sites will include accrediting bodies/auditors, established and emerging cell therapy companies, software developers, professional societies, and the patients who receive these therapies. Active dialogue with government regulators remains essential. Such joint efforts are critical as the number of IEC therapies for myriad oncologic and non-oncologic indications grows.
3.
Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)
Kansagra, A. J., Frey, N. V., Bar, M., Laetsch, T. W., Carpenter, P. A., Savani, B. N., Heslop, H. E., Bollard, C. M., Komanduri, K. V., Gastineau, D. A., et al
Bone marrow transplantation. 2019
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Abstract
On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.
PICO Summary
Population
Children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia
Intervention
Expert opinion on clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia
Comparison
None
Outcome
An initial roadmap for navigating common clinical practice scenarios since the approval of the first commercially available CAR-T product for B-ALL.
4.
Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy
Mahadeo, K. M., Khazal, S. J., Abdel-Azim, H., Fitzgerald, J. C., Taraseviciute, A., Bollard, C. M., Tewari, P., Duncan, C., Traube, C., McCall, D., et al
Nature reviews. Clinical oncology. 2018
Abstract
In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19(+) acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy.