The Changing Landscape of Maintenance Therapy in Newly Diagnosed Multiple Myeloma: A Systematic Review With Network Meta-Analysis of the European Myeloma Network (EMN)

Heinz Ludwig; Evangelos Terpos; Francesca Gay; Niels W C J van de Donk; Sarah Bernhard; Monika Engelhardt; Gordon Cook; Fredrik Schjesvold; Hermann Einsele; Graham Jackson; Charlotte Pawlyn; María-Victoria Mateos; Sonja Zweegman; Martin Schreder; Meral Beksaç; Christoph Driessen; Enrique M Ocio; Rakesh Popat; Leo Rasche; Cyrille Touzeau; Pellegrino Musto; Annemiek Broijl; Meletios Dimopoulos; Roman Hajek; Mario Boccadoro; Pieter Sonneveld

doi:10.1002/ajh.70397

The Changing Landscape of Maintenance Therapy in Newly Diagnosed Multiple Myeloma: A Systematic Review With Network Meta-Analysis of the European Myeloma Network (EMN)

Am J Hematol. 2026 Sep;101(9):2353-2370. doi: 10.1002/ajh.70397. Epub 2026 Jun 18.

Authors

Heinz Ludwig¹, Evangelos Terpos², Francesca Gay³, Niels W C J van de Donk⁴, Sarah Bernhard¹, Monika Engelhardt⁵, Gordon Cook⁶, Fredrik Schjesvold⁷, Hermann Einsele⁸, Graham Jackson⁹, Charlotte Pawlyn^{10

11}, María-Victoria Mateos¹², Sonja Zweegman⁴, Martin Schreder¹³, Meral Beksaç¹⁴, Christoph Driessen¹⁵, Enrique M Ocio¹⁶, Rakesh Popat¹⁷, Leo Rasche⁸, Cyrille Touzeau¹⁸, Pellegrino Musto^{19

20}, Annemiek Broijl²¹, Meletios Dimopoulos^{22

23}, Roman Hajek²⁴, Mario Boccadoro²⁵, Pieter Sonneveld²¹

Affiliations

¹ Wilhelminen Cancer Research Institute, First Department of Medicine, Center for Oncology, Hematology and Palliative Care, Clinic Ottakring, Vienna, Austria.
² Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
³ Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città Della Salute e Della Scienza di Torino, Torino, Italy.
⁴ Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
⁵ Department of Hematology and Oncology, Interdisciplinary Cancer Center and Comprehensive Cancer Center Freiburg, University of Freiburg, Faculty of Freiburg, Freiburg, Germany.
⁶ NIHR Leeds BRC and CRUK Clinical Trials Unit, Leeds Institute of Clinical Trial Research, Leeds, UK.
⁷ Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway.
⁸ Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
⁹ Department of Haematology, Newcastle University, Newcastle, UK.
¹⁰ The Institute of Cancer Research, London, UK.
¹¹ The Royal Marsden Hospital NHS Foundation Trust, London, UK.
¹² Department of Hematology, University Hospital of Salamanca/IBSAL, Salamanca, Spain.
¹³ First Department of Medicine, Center for Oncology, Hematology, and Palliative Care, Clinic Ottakring, Vienna, Austria.
¹⁴ Department of Hematology, Istinye University, Ankara Liv Hospital, Ankara, Turkey.
¹⁵ Department of Oncology/Hematology, Kantonsspital, St. Gallen, Switzerland.
¹⁶ Servicio de Hematología y Hemoterapia, Hospital Universitario Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain.
¹⁷ NIHR/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK.
¹⁸ Service D'hématologie Clinique, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France.
¹⁹ Department of Precision and Regenerative Medicine and Ionian Area, "Aldo Moro" University School of Medicine, Bari, Italy.
²⁰ Unit of Hematology and Stem Cell Transplantation, AOU Consorziale Policlinico, Bari, Italy.
²¹ Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
²² Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece.
²³ Department of Medicine, Korea University, Seoul, Republic of Korea.
²⁴ FN Ostrava, Ostrava, Czech Republic.
²⁵ European Myeloma Network (EMN), Torino, Italy.

Abstract

We performed a comprehensive review with meta- and network meta-analyzes of maintenance-therapy studies. Lenalidomide, proteasome inhibitors, and CD38 antibodies improved progression-free survival (PFS). However, overall survival (OS) benefit appeared only with lenalidomide in transplant-eligible (TE) patients, while CD38-directed therapy showed a trend toward improved OS not seen with proteasome inhibitors. The network meta-analysis ranked regimens against observation: daratumumab-lenalidomide (DR) yielded the greatest PFS benefit, followed by carfilzomib-lenalidomide-dexamethasone (KRd), KR in TE, and DRd in transplant-ineligible patients. Significant OS prolongation in TE patients occurred with KR, DR, and lenalidomide alone.

Publication types

Systematic Review
Network Meta-Analysis
Review

MeSH terms

Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / therapeutic use
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Dexamethasone / administration & dosage
Dexamethasone / therapeutic use
Europe
Humans
Lenalidomide / administration & dosage
Lenalidomide / therapeutic use
Maintenance Chemotherapy* / methods
Multiple Myeloma* / diagnosis
Multiple Myeloma* / drug therapy
Multiple Myeloma* / mortality
Oligopeptides / administration & dosage
Oligopeptides / therapeutic use
Progression-Free Survival
Proteasome Inhibitors / therapeutic use

Substances

Lenalidomide
Dexamethasone
carfilzomib
Oligopeptides
Antibodies, Monoclonal
daratumumab
Proteasome Inhibitors

Grants and funding

Austrian Forum Against Cancer