Abstract
In the past 15 years, significant improvements in overall survival have been observed in multiple myeloma (MM), mainly due to the availability of novel drugs with variable mechanisms of action. However, these improvements do not benefit all patients, and some of them, defined as high risk, still display short survival. The most important risk factors are the genetic abnormalities present in the malignant plasma cells. The most important high-risk features are the del(17p), the del(1p32), the t(4;14), and 1q gains. Assessing these markers is mandatory at diagnosis and at least at first relapse, since it has been clearly shown that the lenalidomide-dexamethasone combination is not efficient in these high-risk patients. In contrast, a triplet combination adding a proteasome inhibitor or a monoclonal antibody to the lenalidomide-dexamethasone backbone clearly improves the survival. Another way to improve the outcome would be to specifically target genetic abnormalities with specific inhibitors. The sequencing of more than 1,000 MM exomes revealed again a huge heterogeneity. The most frequent mutations involve the KRAS and NRAS genes (20%-25% each). However, to date, no good RAS-inhibitors are clinically available, preventing target...Continue Reading
References
Nov 16, 2002·Blood·Madhumita SantraJohn Shaughnessy
Jun 14, 2003·Blood·Rafael FonsecaPhilip R Greipp
Apr 6, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philip R GreippJan Westin
May 18, 2006·Blood·Ichiro HanamuraJohn D Shaughnessy
Jan 9, 2007·Blood·Hervé Avet-LoiseauClaire Mathiot
Aug 30, 2008·The New England Journal of Medicine·Jesús F San MiguelUNKNOWN VISTA Trial Investigators
Jul 17, 2010·Haematologica·Laurence LodéHervé Avet-Loiseau
Jul 21, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hervé Avet-LoiseauJean-Luc Harousseau
Mar 18, 2011·The New England Journal of Medicine·Antonio Palumbo, Kenneth Anderson
Mar 25, 2011·Nature·Michael A ChapmanTodd R Golub
Jul 14, 2011·Blood·Jeremy T LarsenS Vincent Rajkumar
Feb 4, 2012·Cancer Research·Jill CorrePhilippe Bourin
May 2, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hervé Avet-LoiseauPhilippe Moreau
Oct 4, 2012·Leukemia·H Avet-LoiseauUNKNOWN International Myeloma Working Group
Jan 16, 2013·Cell Reports·Ludmil B AlexandrovMichael R Stratton
Feb 7, 2013·British Journal of Haematology·Josefina UdiMonika Engelhardt
Mar 16, 2013·Hematological Oncology·Anna YordanovaIngo G H Schmidt-Wolf
Apr 25, 2013·Cancer Discovery·Mindaugas AndrulisMarc S Raab
Jan 17, 2014·Nature Communications·Niccolo BolliNikhil C Munshi
Jan 18, 2014·Cancer Cell·Jens G LohrTodd R Golub
Mar 22, 2014·Blood·Joaquin Martinez-LopezRamón García-Sanz
Jun 4, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philippe MoreauJean-Yves Mary
Jun 11, 2014·Cancer Medicine·Gordan SrkalovicBart Barlogie
Dec 9, 2014·The New England Journal of Medicine·A Keith StewartUNKNOWN ASPIRE Investigators
Jun 3, 2015·The New England Journal of Medicine·Sagar LonialUNKNOWN ELOQUENT-2 Investigators
Aug 1, 2015·Leukemia·C J HeuckG Morgan
Aug 5, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonio PalumboPhilippe Moreau
Aug 19, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian A WalkerGareth J Morgan
Oct 31, 2015·Blood·Marie-Lorraine ChretienHervé Avet-Loiseau
Mar 17, 2016·Nature·Yu LiuScott W Lowe
Apr 28, 2016·The New England Journal of Medicine·Philippe MoreauUNKNOWN TOURMALINE-MM1 Study Group
Aug 25, 2016·The New England Journal of Medicine·Antonio PalumboUNKNOWN CASTOR Investigators
Oct 6, 2016·The New England Journal of Medicine·Meletios A DimopoulosUNKNOWN POLLUX Investigators
Jul 8, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philippe MoreauFrançoise Kraeber-Bodere
Oct 12, 2017·Blood·Shaji KumarCyrille Touzeau
Citations
Jul 25, 2019·American Journal of Hematology·Irit AviviArtur Jurczyszyn
Jul 21, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mehmet Kemal SamurNikhil C Munshi
Sep 29, 2019·British Journal of Cancer·Heinz LudwigNiklas Zojer
May 28, 2019·Current Oncology Reports·Crystal Antoine-Pepeljugoski, Marc Justin Braunstein
Dec 4, 2019·Scientific Reports·Umair MunawarThorsten Stühmer
Jun 15, 2019·Acta Pharmacologica Sinica·Xue-Han ChenTie Zhang
Jul 15, 2020·Journal for Immunotherapy of Cancer·Nina ShahMadhav Dhodapkar
Jul 25, 2020·Haematologica·Annamaria Gulla, Kenneth C Anderson
Dec 2, 2020·Cancers·Titouan CazaubielAurore Perrot
Oct 16, 2020·Haematologica·Annamaria Gulla, Kenneth C Anderson
May 22, 2021·Frontiers in Immunology·Catherine OukChristelle Vincent-Fabert
Dec 24, 2020·Acta Clinica Belgica·Marie-Christiane VekemansNathalie Meuleman