TY - JOUR
T1 - Chimeric Antigen Receptor T Cell Therapy versus Hematopoietic Stem Cell Transplantation
T2 - An Evolving Perspective
AU - Goldsmith, Scott R.
AU - Ghobadi, Armin
AU - Dipersio, John F.
AU - Hill, Brian
AU - Shadman, Mayzar
AU - Jain, Tania
N1 - Funding Information:
Financial disclosure: Supported by a National Cancer Institute Outstanding Investigator Award (R35 CA210084; PI: J.F.D.). Conflict of interest statement: S.R.G.: consulting/advisory boards: Janssen, Sanofi-Genzyme, Wugen, Oncovalent; travel: Adaptive Biosciences; research support: Adaptive Biosciences. A.G.: research support: Kite Pharma-Gilead and Amgen; advisory board member/consultant: Kite Pharma-Gilead, Amgen, Celgene, EUSA, Atara, CRISPR Therapeutics, and Wugen. J.F.D.: consulting/advisory committee: Rivervest; research collaboration: Bioline, Incyte, NeoImmuneTech, Macrogenic; employment/salary: Washington University; ownership-equity: Magenta and Wugen. B.H.: research funding: Gilead, BMS; consulting: Gilead, BMS, Novartis. M.S.: consulting, advisory board, steering committee or data safety monitoring committee: AbbVie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys/Incyte, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio, Regeneron, Merck, Fate Therapeutics, and Atara Biotherapeutics; research funding: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, AbbVie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, Genmab, and Morphosys/Incyte. T.J.: institutional research support: CTI Biopharma, SyneosHealth, Incyte; consultancy: Targeted Healthcare Communications; advisory board: Care Dx, Bristol Myers Squibb, Incyte, AbbVie, and CTI. Financial disclosure: See Acknowledgments on page XXX.
Funding Information:
Financial disclosure: Supported by a National Cancer Institute Outstanding Investigator Award (R35 CA210084; PI: J.F.D.).
Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy
PY - 2022
Y1 - 2022
N2 - Cellular therapy modalities, including autologous (auto-) hematopoietic cell transplantation (HCT), allogeneic (allo-) HCT, and now chimeric antigen receptor (CAR) T cell therapy, have demonstrated long-term remission in advanced hematologic malignancies. Auto-HCT and allo-HCT, through hematopoietic rescue, have permitted the use of higher doses of chemotherapy. Allo-HCT also introduced a nonspecific immune-mediated targeting of malignancy resulting in protection from relapse, although at the expense of similar targeting of normal host cells. In contrast, CAR T therapy, through genetically engineered immunotherapeutic precision, allows for redirection of autologous immune effector cells against malignancy in an antigen-specific and MHC-independent fashion, with demonstrated efficacy in patients who are refractory to cytotoxic chemotherapy. It too has unique toxicities and challenges, however. Non-Hodgkin lymphoma (including large B cell lymphoma, mantle cell lymphoma, and follicular lymphoma), B cell acute lymphoblastic leukemia, and multiple myeloma are the 3 main diseases associated with the use of fully developed CAR T products with widespread deployment. Recent and ongoing clinical trials have been examining the interface among the 3 cellular therapy modalities (auto-HCT, allo-HCT, and CAR T) to determine whether they should be “complementary” or “competitive” therapies. In this review, we examine the current state of this interface with respect to the most recent data and delve into the controversies and conclusions that may inform clinical decision making.
AB - Cellular therapy modalities, including autologous (auto-) hematopoietic cell transplantation (HCT), allogeneic (allo-) HCT, and now chimeric antigen receptor (CAR) T cell therapy, have demonstrated long-term remission in advanced hematologic malignancies. Auto-HCT and allo-HCT, through hematopoietic rescue, have permitted the use of higher doses of chemotherapy. Allo-HCT also introduced a nonspecific immune-mediated targeting of malignancy resulting in protection from relapse, although at the expense of similar targeting of normal host cells. In contrast, CAR T therapy, through genetically engineered immunotherapeutic precision, allows for redirection of autologous immune effector cells against malignancy in an antigen-specific and MHC-independent fashion, with demonstrated efficacy in patients who are refractory to cytotoxic chemotherapy. It too has unique toxicities and challenges, however. Non-Hodgkin lymphoma (including large B cell lymphoma, mantle cell lymphoma, and follicular lymphoma), B cell acute lymphoblastic leukemia, and multiple myeloma are the 3 main diseases associated with the use of fully developed CAR T products with widespread deployment. Recent and ongoing clinical trials have been examining the interface among the 3 cellular therapy modalities (auto-HCT, allo-HCT, and CAR T) to determine whether they should be “complementary” or “competitive” therapies. In this review, we examine the current state of this interface with respect to the most recent data and delve into the controversies and conclusions that may inform clinical decision making.
KW - Allogeneic HCT
KW - ASCT
KW - B-cell ALL
KW - CAR T
KW - Multiple myeloma
KW - Non-Hodgkin lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85137028795&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2022.07.015
DO - 10.1016/j.jtct.2022.07.015
M3 - Review article
C2 - 35878743
AN - SCOPUS:85137028795
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
SN - 2666-6367
ER -