title: 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau.
abstract: In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark. christian.winther.eskelund.01@regionh.dk.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Eskelund
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Kolstad
authors.affiliation: Department of Oncology, Lund University Hospital, Lund, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Jerkeman
authors.affiliation: Department of Haematology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Räty
authors.affiliation: Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Laurell
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Eloranta
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Smedby
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Husby
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lone B
authors.initials: LB
authors.lastname: Pedersen
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels S
authors.initials: NS
authors.lastname: Andersen
authors.affiliation: Department of Oncology, Lund University Hospital, Lund, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Department of Haematology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.affiliation: Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Bentzen
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Kuittinen
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Grete F
authors.initials: GF
authors.lastname: Lauritzsen
authors.affiliation: Section of Haematology and Coagulation Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Herman
authors.initials: H
authors.lastname: Nilsson-Ehle
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiaer
authors.affiliation: Department of Pathology, Lund University Hospital, Lund, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Ehinger
authors.affiliation: Department of Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.affiliation: Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.affiliation: Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Karjalainen-Lindsberg
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.|Department of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.|Department of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Garde
authors.affiliation: Department of Haematology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Erkki
authors.initials: E
authors.lastname: Elonen
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Brown
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbaek
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Geisler
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: Mantle Cell Lymphoma; Non-Hodgkin Lymphoma; clinical trials; high dose therapy