Article (Scientific journals)
Treatment of primary plasma cell leukaemia with carfilzomib and lenalidomide-based therapy (EMN12/HOVON-129): final analysis of a non-randomised, multicentre, phase 2 study.
van de Donk, Niels W C J; Minnema, Monique C; van der Holt, Bronno et al.
2023In The Lancet Oncology, 24 (10), p. 1119 - 1133
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Keywords :
Oncology
Abstract :
[en] BACKGROUND: Primary plasma cell leukaemia is a rare and aggressive plasma cell disorder with a poor prognosis. The aim of the EMN12/HOVON-129 study was to improve the outcomes of patients with primary plasma cell leukaemia by incorporating carfilzomib and lenalidomide in induction, consolidation, and maintenance therapy. METHODS: The EMN12/HOVON-129 study is a non-randomised, phase 2, multicentre study conducted at 19 academic centres and hospitals in seven European countries (Belgium, Czech Republic, Denmark, Italy, Norway, The Netherlands, and the UK) for previously untreated patients with primary plasma cell leukaemia aged 18 years or older. Inclusion criteria were newly diagnosed primary plasma cell leukaemia (defined as >2 ×109 cells per L circulating monoclonal plasma cells or plasmacytosis >20% of the differential white cell count) and WHO performance status 0-3. Patients aged 18-65 years (younger patients) and 66 years or older (older patients) were treated in age-specific cohorts and were analysed separately. Younger patients were treated with four 28-day cycles of carfilzomib (36 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 8, 9, 15, 16, 22, and 23). Carfilzomib-lenalidomide-dexamethasone (KRd) induction was followed by double autologous haematopoietic stem-cell transplantation (HSCT), four cycles of KRd consolidation, and then maintenance with carfilzomib (27 mg/m2 intravenously on days 1, 2, 15, and 16 for the first 12 28-day cycles, and then 56 mg/m2 on days 1 and 15 in all subsequent cycles) and lenalidomide (10 mg orally on days 1-21) until progression. Patients who were eligible for allogeneic HSCT, could also receive a single autologous HSCT followed by reduced-intensity conditioning allogeneic HSCT and then carfilzomib-lenalidomide maintenance. Older patients received eight cycles of KRd induction followed by maintenance therapy with carfilzomib and lenalidomide until progression. The primary endpoint was progression-free survival. The primary analysis population was the intention-to-treat population, irrespective of the actual treatment received. Data from all participants who received any study drug were included in the safety analyses. The trial was registered at www.trialregister.nl (until June 2022) and https://trialsearch.who.int/ as NTR5350; recruitment is complete and this is the final analysis. FINDINGS: Between Oct 23, 2015, and Aug 5, 2021, 61 patients were enrolled and received KRd induction treatment (36 patients aged 18-65 years [20 (56%) were male and 16 (44%) female], and 25 aged ≥66 years [12 (48%) were male and 13 (52%) female]). With a median follow-up of 43·5 months (IQR 27·7-67·8), the median progression-free survival was 15·5 months (95% CI 9·4-38·4) for younger patients. For older patients, median follow-up was 32·0 months (IQR 24·7-34·6), and median progression-free survival was 13·8 months (95% CI 9·2-35·5). Adverse events were most frequently observed directly after treatment initiation, with infections (two of 36 (6%) younger patients and eight of 25 (32%) older patients) and respiratory events (two of 36 [6%] younger patients and four of 25 [16%] older patients) being the most common grade 3 or greater events during the first four KRd cycles. Treatment-related serious adverse events were reported in 26 (72%) of 36 younger patients and in 19 (76%) of 25 older patients, with infections being the most common. Treatment-related deaths were reported in none of the younger patients and three (12%) of the older patients (two infections and one unknown cause of death). INTERPRETATION: Carfilzomib and lenalidomide-based therapy provides improved progression-free survival compared with previously published data. However, results remain inferior in primary plasma cell leukaemia compared with multiple myeloma, highlighting the need for new studies incorporating novel immunotherapies. FUNDING: Dutch Cancer Society, Celgene (a BMS company), and AMGEN.
Disciplines :
Hematology
Author, co-author :
van de Donk, Niels W C J;  Department of Hematology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. Electronic address: n.vandedonk@amsterdamumc.nl
Minnema, Monique C;  University Medical Center Utrecht, Department of Hematology, Utrecht University, Utrecht, Netherlands
van der Holt, Bronno;  HOVON Foundation, Rotterdam, Netherlands, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
Schjesvold, Fredrik;  Oslo Myeloma Center, Department of Hematology, Oslo University Hospital and KG Jebsen Center for B cell malignancies, University of Oslo, Oslo, Norway
Wu, Ka Lung;  Department of Hematology, ZNA Stuivenberg, Antwerp, Belgium
Broijl, Annemiek;  Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
Roeloffzen, Wilfried W H;  Department of Hematology, University Medical Center Groningen, University Groningen, Groningen, Netherlands
Gadisseur, Alain;  Department of Haematology, Antwerp University Hospital, Edegem, Belgium
Pietrantuono, Giuseppe;  Unit of Hematology, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy
Pour, Ludek;  Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
van der Velden, Vincent H J;  Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
Lund, Thomas;  Odense Hospital, Odense, Denmark
Offidani, Massimo;  AOU Ospedali Riuniti di Ancona, Ancona, Italy
Grasso, Mariella;  Azienda Ospedaliera S Croce e Carle, Cuneo, Italy
Giaccone, Luisa;  Department of Oncology and Hematology, SSD Stem Cell Transplant Center, AOU Citta della Salute e della Scienza di Torino, Torino, Italy
Razawy, Wida;  HOVON Foundation, Rotterdam, Netherlands
Tacchetti, Paola;  IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematolgia Seràgnoli, Bologna, Italy
Mancuso, Katia;  IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematolgia Seràgnoli, Bologna, Italy, Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
Silkjaer, Trine;  Aarhus University Hospital, Aarhus, Denmark
Caers, Jo  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique
Zweegman, Sonja;  Department of Hematology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
Hájek, Roman;  Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic, Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
Benjamin, Reuben;  King's College Hospital, London, UK
Vangsted, Annette Juul;  Department of Hematology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
Boccadoro, Mario;  European Myeloma Network, Torino, Italy
Gay, Francesca;  Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
Sonneveld, Pieter;  Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
Musto, Pellegrino;  Department of Precision and Regenerative Medicine and Ionian Area, Aldo Moro University School of Medicine, and Hematology and Stem Cell Transplantation Unit, AOU Consorziale Policlinico, Bari, Italy
More authors (18 more) Less
Language :
English
Title :
Treatment of primary plasma cell leukaemia with carfilzomib and lenalidomide-based therapy (EMN12/HOVON-129): final analysis of a non-randomised, multicentre, phase 2 study.
Publication date :
October 2023
Journal title :
The Lancet Oncology
ISSN :
1470-2045
eISSN :
1474-5488
Publisher :
Elsevier Ltd, England
Volume :
24
Issue :
10
Pages :
1119 - 1133
Peer reviewed :
Peer Reviewed verified by ORBi
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