Key clinical point: Unintentional transduction of a single leukemic B cell induced resistance to CTL019 (tisagenlecleucel) therapy.
Major finding: A patient with B-cell acute lymphoblastic leukemia (B-ALL) had frank relapse 9 months after a CTL019 infusion, with more than 90% bone marrow infiltration of chimeric antigen receptor–transduced B-cell leukemia cells.
Study details: A case study of a 20-year-old male with B-ALL undergoing CTL019 therapy.
Disclosures: Study funding was provided by Bristol-Myers Squibb, Novartis, the National Institutes of Health, and others. Dr. Ruella and several of his colleagues work under a research collaboration involving the University of Pennsylvania and the Novartis Institutes of Biomedical Research and are inventors of intellectual property licensed by the University of Pennsylvania to Novartis.
Ruella M et al. Nat Med. 2018 Oct 1. doi: 10.1038/s41591-018-0201-9.
Must Reads in ALL
Tisagenlecleucel responses persist at 18 months in r/r B-cell ALL, Grupp SA et al. ASH 2018, Abstract 895
Immune system changes play a role in AML relapse, Christopher MJ et al. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1808777.
CAR T-cell cost effectiveness in ALL, Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530
CAR T induced resistance in ALL, Ruella M et al. Nat Med. 2018 Oct 1. doi: 10.1038/s41591-018-0201-9
ALL complications carry cognitive risks, Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.