European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma
Benedetto Bruno,
Ralph Wäsch,
Monika Engelhardt,
Francesca Gay,
Luisa Giaccone,
Mattia D’Agostino,
Luis-Gerardo Rodríguez-Lobato,
Sophia Danhof,
Nico Gagelmann,
Nicolaus Kröger,
Rakesh Popat,
Niels W.C.J. van de Donk,
Evangelos Terpos,
Meletios A. Dimopoulos,
Pieter Sonneveld,
Hermann Einsele,
Mario Boccadoro
Affiliations
Benedetto Bruno
Department 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; Division of Hematology and Medical Oncology, Perlmutter Cancer Center, Grossman School of Medicine, NYU Langone Health, New York, NY
Ralph Wäsch
Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg
Monika Engelhardt
Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg
Francesca Gay
Department 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
Luisa Giaccone
Department 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
Mattia D’Agostino
Department 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
Luis-Gerardo Rodríguez-Lobato
Unit of Amyloidosis and Multiple Myeloma, Department of Hematology, Hospital Clínic of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Division of Medicine II, University Hospital Würzburg, Würzburg
Sophia Danhof
Division of Medicine II, University Hospital Würzburg, Würzburg
Nico Gagelmann
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg
Nicolaus Kröger
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg
Rakesh Popat
Department of Hematology, University College London Hospitals, London
Niels W.C.J. van de Donk
Department of Hematology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Location VUmc, Amsterdam
Evangelos Terpos
Stem Cell Transplantation Unit, Plasma Cell Dyscrasias Unit, Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens
Meletios A. Dimopoulos
Stem Cell Transplantation Unit, Plasma Cell Dyscrasias Unit, Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens
Pieter Sonneveld
Erasmus MC Cancer Institute, Rotterdam
Hermann Einsele
Division of Medicine II, University Hospital Würzburg, Würzburg
Mario Boccadoro
Department 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
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, treatment 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.
