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Ferrata Storti Foundation
Haematologica 2021 Volume 106(8):2054-2065
European Myeloma Network perspective on CAR T-cell therapies for multiple myeloma
Benedetto Bruno,1,2o Ralph Wäsch,3 Monika Engelhardt,3 Francesca Gay,1 Luisa Giaccone,1 Mattia D’Agostino,1 Luis-Gerardo Rodríguez-Lobato,4,5 Sophia Danhof,5 Nico Gagelmann,6 Nicolaus Kröger,6 Rakesh Popat,7 Niels W C J van de Donk,8 Evangelos Terpos,9 Meletios A Dimopoulos,9 Pieter Sonneveld,10 Hermann Einsele5 and Mario Boccadoro1
1Department of Molecular Biotechnology and Health Sciences, University of Torino and Department of Oncology, Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, Presidio Molinette, Torino, Italy; 2Division of Hematology and Medical Oncology, Perlmutter Cancer Center, Grossman School of Medicine, NYU Langone Health, New York, NY, USA; ; 3Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; 4Unit of Amyloidosis and Multiple Myeloma, Department of Hematology, Hospital Clínic of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; 5Division of Medicine II, University Hospital Würzburg, Würzburg, Germany; 6Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 7Department of Hematology, University College London Hospitals, London, UK; 8Department of Hematology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Location VUmc, Amsterdam, the Netherlands; 9Stem Cell Transplantation Unit, Plasma Cell Dyscrasias Unit, Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece and 10Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
oCurrent address: Division of Hematology and Medical Oncology, Perlmutter Cancer Center, Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
ABSTRACT
Chimeric antigen receptor (CAR) T cells (CAR-T) have dramatically changed the treatment landscape of B-cell malignancies, providing a potential cure for relapsed/refractory patients. Long-term responses in patients with acute lymphoblastic leukemia and non Hodgkin lymphomas have encouraged further development in myeloma. In particular, B-cell maturation antigen (BCMA)-targeted CAR-T have established very promising results in heavily pre-treated patients. Moreover, CAR-T targeting other antigens (i.e., SLAMF7 and CD44v6) are currently under investigation. However, none of these current autologous therapies have been approved, and despite high overall response rates across studies, main issues such as long-term outcome, toxicities, treat- ment resistance, and management of complications limit as yet their widespread use. Here, we critically review the most important pre-clinical and clinical findings, recent advances in CAR-T against myeloma, as well as discoveries in the biology of a still incurable disease, that, all together, will further improve safety and efficacy in relapsed/refractory patients, urgently in need of novel treatment options.
Introduction
Recently engineered chimeric antigen receptors (CAR) have greatly increased anti-tumor effects of CAR T cells (CAR-T). Impressive results have been observed with CD19-directed CAR-T in B-cell lymphoproliferative disorders.1-3 In addition, several CAR-T products have been developed for the treatment of multiple myelo- ma (MM). None has yet been approved, and, despite high overall response (OR) across studies, main issues such as long-term outcomes, toxicities and complica- tions need to be solved to allow their widespread clinical use. In this review, the European Myeloma Network (EMN) group aimed to describe the most important pre-clinical and clinical findings, and recent advances in CAR-T technology against MM that may improve their safety and efficacy. Contents, comments and sugges-
Correspondence:
BENEDETTO BRUNO
benedetto.bruno@unito.it
Received: December 7, 2020. Accepted: March 11, 2021. Pre-published: April 1, 2021.
https://doi.org/10.3324/haematol.2020.276402
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