Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.

1st Department of Internal Medicine Semmelweis University Budapest Hungary

Department of Haematology Freeman Hospital Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle Upon Tyne United Kingdom

Department of Haematology Université Catholique de Louvain CHU UCL Namur Yvoir Belgium

Department of Hemato Oncology Palacký University and University Hospital Olomouc Czech Republic

Department of Hematology and Oncology Paracelcus Medical University Klinikum Nürnberg Nürnberg Germany

Department of Hematology Institut Catalá d'Oncologia Hospital Duran i Reynals Universitat de Barcelona Barcelona Spain

Department of Hematology Vall d'Hebron Institute of Oncology Vall d'Hebron University Hospital Barcelona Spain

Department of Internal Medicine Arthur G James Comprehensive Cancer Center Ohio State University Wexner Medical Center Columbus OH USA

Department of Medicine 3 LMU University Hospital Munich Germany

Department of Medicine Ronald Reagan UCLA Medical Center Santa Monica CA USA

Division of Hematology Department of Translational Medicine University of Eastern Piedmont Novara Italy

Hématologie Hospices Civils de Lyon and Université de Lyon Lyon France

Institute of Pathology University of Würzburg Würzburg Germany

Maria Sklodowska Curie National Research Institute of Oncology Kraków Poland

Medizinische Klinik und Poliklinik 2 Universitätsklinik Würzburg Würzburg Germany

Molecular and Clinical Cancer Medicine University of Liverpool and The Clatterbridge Cancer Centre Liverpool United Kingdom

MorphoSys AG Planegg Germany

Service d'Hématologie Clinique et de Thérapie Cellulaire CHU Estaing Clermont Ferrand France

Università degli Studi di Perugia Azienda Ospedaliera Santa Maria di Terni Terni Italy

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NCT02399085