Multiple myeloma (MM) is a heterogenous malignant disease. Novel agents including bispecific antibodies and chimeric antigen receptor (CAR) T cells have improved response rates and patient outcome, but the majority of patients ultimately still relapse. High dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) remains standard care of treatment for transplant-eligible patients. While single auto-HCT is commonly used, a planned tandem auto-HCT or auto-allo approach remains controversial, based on conflicting results from clinical trials. Here we compared the outcome of 24,936 MM patients aged between 20 and 65 years who underwent first auto-HCT during 2002-2015, reported to the EBMT registry, of whom 3683 and 878 got tandem auto-HCT and auto-allo-HCT respectively. We used non-standard statistical approaches to account for time-dependence of treatments and of their effects, including models with multiple timescales and dynamic prediction. Differences were reported by graphs of hazard functions, hazard ratios and conditional probabilities over time. For both OS and PFS, there was a limited but persistent advantage for the tandem auto-HCT group compared to single auto-HCT, and a clear advantage for the auto-allo-HCT group over both other strategies in the longer term, albeit at the cost of higher early mortality.

Ankara Liv Hospital Istinye University Ankara Turkey

Birmingham Centre for Cellular Therapy and Transplant Birmingham United Kingdom

Christie Hospital Manchester Manchester United Kingdom

CHU de Lille Univ Lille INSERM U1286 Infinite Lille France

CHU Nantes Nantes France

Dél pesti Centrumkórház Budapest Hungary

Department of Haematology Trinity College Dublin St James's Hospital Dublin Ireland

Department of Haematology University College London Hospitals NHS Trust London UK

EBMT Leiden Study Unit Leiden the Netherlands

Erasmus MC Cancer Institute Rotterdam Netherlands

Kings College Hospital London London United Kingdom

Newcastle upon Tyne Hospitals Newcastle United Kingdom

Oslo University Hospital Rikshospitalet Oslo Norway

Royal Marsden Hospital London United Kingdom

Sapienza University of Rome Rome Italy

St Bartholomew's Hospital London London United Kingdom

Transplantation and Cellular Therapy Department of Hematology Institut Paoli Calmettes Management Sport Cancer Lab Luminy Aix Marseille University Marseille France

University Clinical Centre Medical University of Warsaw Warsaw Poland

University Hospital Brno Brno Czech Republic

University Hospital Eppendorf Hamburg Germany

University Hospital of Heidelberg Medical Department 5 Heidelberg Germany

University of Muenster Muenster Germany

VU University Medical Center Amsterdam Netherlands

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