The randomized phase III TRIANGLE trial of the European MCL network is the largest study ever conducted in MCL.

The trial evaluated the addition of ibrutinib to a standard ASCT containing treatment (arm A+I) in comparison to standard treatment (arm A) and to an ibrutinib containing treatment without ASCT (arm I). 870 patients from 13 countries with untreated, stage II-IV MCL were enrolled.The study included regular MRD analyses with collection of baseline and multiple follow-up samples, generating a large tissue and plasma collection for translational studies. Moreover, FFPE tissues from most patients are available for additional histopatological testing.

Therefore, TRIANGLE is a unique opportunity for multilayer characterization of a large patient cohort treated with the new standard of care. MULTIPLY will generate and validate an integrative model of various clinico-biological baseline and dynamic follow-up parameters. Based on functional analysis we will also identify potential new therapeutic targets.


MULTIPLY is structured into 3 major interconnected workpackages (WP):

a) Identification of clinical predictors, characterization of relapses and salvage treatment (Clinical project);

b) Identification of lymph node derived predictors (Lymph node WP);

c) Evaluation of biological predictors based on PB, BM and cfDNA (Liquid tissue WP).


All information will be integrated to generate a multilayer model of prediction incorporating all available clinical and biological markers.

 Multiply involved researchers

Martin Dreyling
Department of Medicine III, Ludwig-Maximilians-University Hospital, Munich, Germany


Sílvia Beà
Hematology and Hematopathology Departments, Hospital Clínic Barcelona, Barcelona, Spain, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain


Marco Ladetto
Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy "SS Antonio e Biagio e Cesare Arrigo" Hospital, Alessandria, Italy


Stefan Alig
Laboratory of Ash A. Alizadeh Division of Oncology, Stanford University School of Medicine


Elias Campo
Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain


Francesca Cordero
Department of Computer Science, University of Torino, Torino, Italy


Sara Ek
Department of Immunotechnology, Lund University, Lund, Sweden


Simone Ferrero
Unit of Hematology, Department of Biotechnology and Health Sciences, University of Torino, Torino, Italy; Hematology Division 1U, "AOU Città della Salute e della Scienza di Torino", Torino, Italy


Eva Ginè
Department of Hematology, GELTAMO, Hospital Clínic of Barcelona, Barcelona, Spain


Georg Hess
Department of Hematology, Oncology and Pneumology, Comprehensive Cancer Center, University Medical School of the Johannes Gutenberg-University, Mainz, Germany

Eva Hoster
Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany


Mats Jerkeman
Department of Oncology, Lund University Hospital, Lund, Sweden


Wolfram Klapper
Department of Pathology, Haematopathology Section and Lymph Node Registry, University of Kiel/University Hospital Schleswig-Holstein, Kiel, Germany


Pavel Klener
First Department of Internal Medicine - Department of Hematology, University General Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic. Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic


Thomas Oellerich
Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Frankfurt, Germany


Christiane Pott
Medical Department II, University Hospital Schleswig-Holstein, Kiel, Germany


Hilka Rauert-Wunderlich
Institute of Pathology, University of Würzburg and Comprehensive Cancer Center(CCC) Mainfranken, Würzburg, Germany


Andreas Rosenwald
Institute of Pathology, University of Würzburg and Comprehensive Cancer Center(CCC) Mainfranken, Würzburg, Germany


Elisabeth Silkenstedt
Department of Hematology and Oncology, Ludwig-Maximilians-University Hospital, Munich, Germany