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Ferrata Storti Foundation
Haematologica 2019 Volume 104(12):2358-2360
Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network
Philippe Moreau,1 Pieter Sonneveld,2 Mario Boccadoro,3 Gordon Cook,4 Ma Victoria Mateos,5 Hareth Nahi,6 Hartmut Goldschmidt,7 Meletios A. Dimopoulos,8 Paulo Lucio,9 Joan Bladé,10 Michel Delforge,11 Roman Hajek,12 Heinz Ludwig,13 Thierry Facon,14 Jesus F. San Miguel15 and Hermann Einsele16
1University Hospital Hôtel-Dieu, Nantes, France; 2Erasmus Medical Center, Rotterdam, the Netherlands; 3Università di Torino/Azienda Ospedaliera San Giovanni, Torino, taly; 4Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK; 5University of Salamanca, Salamanca, Spain; 6Karolinska Institutet, Stockholm, Sweden; 7Universitätsklinikum Heidelberg, Heidelberg, Germany; 8University Athens School of Medicine, Athens, Greece; 9Fundação Champalimaud, Lisbon, Portugal; 10Hospital Clinic de Barcelona, Barcelona, Spain; 11Department of Hematology, Catholic University of Leuven, Leuven, Belgium; 12University of Ostrava, Ostrava, Czech Republic; 13Wilhelminen Cancer Research Institute, Wilhelminen, Austria; 14University Hospital Hurriez, Lille, France; 15University of Navarra, Navarra, Spain and 16University of Wurzburg, Wurzburg, Germany
ABSTRACT
Adoptive cellular therapy using chimeric antigen receptor T-cell (CAR- T) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell pro- grams now being tested in clinical trials are targeting B-cell maturation anti- gen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodula- tory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refrac- tory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical con- siderations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development.
Introduction
In recent years, the development of immunotherapy has revolutionized the treat- ment of cancer, including hematologic malignancies and multiple myeloma (MM).1 Therapeutic agents which induce the autologous immune cells to mediate tumor cell killing and to overcome the immunosuppressive mechanisms of the tumor microenvironment may improve clinical outcome. In this setting, adoptive cellular therapy using chimeric antigen receptor (CAR-T), a redirection strategy of T cells with the goal of increasing the frequency of tumor-directed and functionally active T cells targeting specifically expressed antigens on myeloma cells, is currently being evaluated in patients with MM.2
CAR-T cell therapy has already been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of relapsed / refractory B-cell acute lymphoblastic leukemia (B-ALL) in pediatric and young adult patients, and for diffuse large B-cell lymphoma (DLBCL). At the time of writing (2019), it is under evaluation for the treatment of relapsed / refractory MM (RRMM) in phase I / II trials3 and phase III trials sponsored by different pharmaceu- tical companies have just started in these patients. Therefore, CAR-T cell therapy will not have been approved for the treatment of MM by the end of 2019.
B-cell maturation antigen (BCMA, also named TNFRSF17 or CD269) belongs to the family of tumor necrosis factors. It was initially identified on the cell surface of
Correspondence:
PHILIPPE MOREAU
philippe.moreau@chu-nantes.fr
Received: April 24, 2019. Accepted: August 21, 2019. Pre-published: August 22, 2019.
doi:10.3324/haematol.2019.224204
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/12/2358
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