Biology of Disease Relapse in Myeloid Disease: Implication for Strategies to Prevent and Treat Disease Relapse After Stem-Cell Transplantation.

Abstract

Article Tools REVIEW ARTICLES Immunotherapy for Hematologic Malignancies Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.20.01587 Journal of Clinical Oncology - published online before print January 12, 2021 PMID: 33434062 Biology of Disease Relapse in Myeloid Disease: Implication for Strategies to Prevent and Treat Disease Relapse After Stem-Cell Transplantation Joseph C. Rimando, MD1xJoseph C. RimandoSearch for articles by this author; Matthew J. Christopher, MD, PhD1xMatthew J. ChristopherSearch for articles by this author; Michael P. Rettig, PhD1xMichael P. RettigSearch for articles by this author; and John F. DiPersio, MD, PhD1xJohn F. DiPersioSearch for articles by this author Show More 1Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO https://doi.org/10.1200/JCO.20.01587 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyCONTEXTKey ObjectiveAcute myeloid leukemia (AML) relapse after allogeneic stem-cell transplantation represents the most common form of treatment failure. This review summarizes recent findings about the mechanisms of AML relapse after transplantation, as well as therapies to prevent or treat post-transplant relapse.Knowledge GeneratedAML relapse after transplantation is associated with several factors, including active disease before transplantation, conditioning intensity, loss of antigen presentation by relapsing AML cells, and immune cell exhaustion. Studies of post-transplantation maintenance, either with hypomethylating agents or tyrosine kinase inhibitors, have shown some encouraging results. However, standard strategies to treat overt relapse with chemotherapy or donor lymphocyte infusion rarely result in long-term disease control.RelevanceNew therapies to prevent or treat AML relapse after transplantation are urgently needed. Strategies to reverse or circumvent immune escape by AML cells—for example, by using bispecific T cell–engaging molecules—may prove effective in this regard.SUPPORTSupported by grants from the NIH/NCI: K08 Program grant (CA222630-01, to M.J.C.), NCI Research Specialist Awards (R50 CA211466, to M.P.R.), a Genomics of Acute Myeloid Leukemia Program Project grant (P01 CA101937, to J.F.D.), an NCI Outstanding Investigator Award (R35 CA197561, to J.F.D.), and a Specialized Program of Research Excellence in Acute Myeloid Leukemia grant (P50 CA171963, to J.F.D.).AUTHOR CONTRIBUTIONSConception and design: All authorsFinancial support: John F. DiPersioAdministrative support: John F. DiPersioProvision of study materials or patients: John F. DiPersioCollection and assembly of data: Joseph C. Rimando, John F. DiPersio, Matthew J. Christopher, Michael P. RettigData analysis and interpretation: Joseph C. Rimando, Michael P. Rettig, John F. DiPersio, Matthew J. ChristopherManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTBiology of Disease Relapse in Myeloid Disease: Implication for Strategies to Prevent and Treat Disease Relapse After Stem-Cell TransplantationThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I =Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Joseph C. RimandoStock and Other Ownership Interests: MerckMichael P. RettigConsulting or Advisory Role: RivervestResearch Funding: MacroGenics, Amphivena Therapeutics, Maxcyte, BiolineRxPatents, Royalties, Other Intellectual Property: MPR has pending patent applications (PCT/US2017/059777, integrin inhibitors and chemokine receptor agents; PCT/US2017/059733, integrin antagonists) and reports royalties received from the patent applications during the conduct of the studyJohn F. DiPersioStock and Other Ownership Interests: Magenta Therapeutics, WUGENHonoraria: IncyteConsulting or Advisory Role: Cellworks, Rivervest, Magenta Therapeutics, IncyteResearch Funding: Amphivena Therapeutics, Macrogenics, Incyte, WUGEN, BiolineRx, Maxcyte, Bigelow AerospacePatents, Royalties, Other Intellectual Property: CD7 and CD2 Knockout for CART to CD7 and CDL, Duvelisib for treatment of cytokine release syndrome (CRS), NT-17 to enhance CART Survival, Novel WU mobilizing compounds, Selection of IMPDH Mutant Stem Cells, IFNg, upregulate MHCII for relapsed AML, Dextran based molecules to detect CAR-T cells, Combining integrin inhibitor with chemokine binders, 016131, JAK and calcineurin inhibition, solid organ transplant, VLA4, gro-b, Triple Combination - CXCR2, VLA-4, gro-b, Targeting IFNR/CSCR3 in GVHD, WU/SLU compounds VLA4 and CXCR2Travel, Accommodations, Expenses: Incyte, Macrogenics, Magenta TherapeuticsNo other potential conflicts of interest were reported.