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  • Review |

    Chimeric antigen receptor (CAR)-T-cell therapies are showing great promise in the treatment of cancer, particularly B-cell malignancies, but are associated with characteristic, potentially fatal toxicities, principally cytokine-release syndrome, CAR-T-cell-related encephalopathy syndrome, and haemophagocytic lymphohistiocytosis/macrophage-activation syndrome. Herein, the CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising multidisciplinary investigators from various institutions with clinical experience in the use of a range of CAR-T-cell platforms, review these acute toxicities and provide monitoring, grading, and management recommendations.

    • Sattva S. Neelapu
    • , Sudhakar Tummala
    • , Partow Kebriaei
    • , William Wierda
    • , Cristina Gutierrez
    • , Frederick L. Locke
    • , Krishna V. Komanduri
    • , Yi Lin
    • , Nitin Jain
    • , Naval Daver
    • , Jason Westin
    • , Alison M. Gulbis
    • , Monica E. Loghin
    • , John F. de Groot
    • , Sherry Adkins
    • , Suzanne E. Davis
    • , Katayoun Rezvani
    • , Patrick Hwu
    •  & Elizabeth J. Shpall
  • Review |

    Cell-based immunotherapies are showing great promise in the treatment of even the most treatment-refractory of haematological malignancies. Herein, Jennifer Brudno and James Kochenderfer review the results obtained to date with CAR-T-cell therapies for lymphoma. They also discuss what has been learned regarding the limitations of CAR-T-cell therapies and areas for improvement relating to toxicity management, the design of CAR-T-cell products, conditioning regimens, and combination therapies.

    • Jennifer N. Brudno
    •  & James N. Kochenderfer
  • Review |

    A wide range of gene fusions have been detected in solid tumours, and the products of these fusions, some of which result in constitutive activation of kinase signalling, can be targeted using tyrosine-kinase inhibitors. However, the development of acquired resistance is almost inevitable. In this Review, the authors describe strategies used to diagnose and treat patients with fusion-positive cancers.

    • Alison M. Schram
    • , Matthew T. Chang
    • , Philip Jonsson
    •  & Alexander Drilon
  • Review |

    The development of predictive biomarkers is complex and the non-systematic approach to biomarker development in HER2-positive breast cancer challenges the way translational research is performed. Women with very favourable prognostic features will likely prefer shorter courses of treatment and might enquire about the possibility to forego aggressive chemotherapy. Considering these legitimate needs, Gingras et al. review the results of more than a decade of translational research efforts in this disease.

    • Isabelle Gingras
    • , Géraldine Gebhart
    • , Evandro de Azambuja
    •  & Martine Piccart-Gebhart
  • Review |

    Virtually all successful treatments of cancer either create, restore or enhance the antitumour immune response. Therefore, the specific features of the immune microenvironment, both before and after treatment, are important determinants of patients' outcomes. In this Review, the authors describe the influence of the immunological characteristics of the tumour microenvironment on responses to treatment in patients with a variety of cancers.

    • Wolf H. Fridman
    • , Laurence Zitvogel
    • , Catherine Sautès–Fridman
    •  & Guido Kroemer

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