BACKGROUND: Patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for autologous stem-cell transplantation have poor outcomes and few treatment options. Tafasitamab (MOR208) is an Fc-enhanced, humanised, anti-CD19 monoclonal antibody that has shown preclinical and single-agent activity in patients with relapsed or refractory B-cell malignancies. Preclinical data suggested that tafasitamab might act synergistically with lenalidomide. We aimed to assess the antitumour activity and safety of tafasitamab plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for autologous stem-cell transplantation. METHODS: In this multicentre, open-label, single-arm, phase 2 study (L-MIND), patients older than 18 years with histologically confirmed diffuse large B-cell lymphoma, who relapsed or had refractory disease after previous treatment with one to three systemic regimens (with at least one anti-CD20 therapy), were not candidates for high-dose chemotherapy and subsequent autologous stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0-2, and had measurable disease at baseline were recruited from 35 academic and community hospitals in ten countries. Patients received coadministered intravenous tafasitamab (12 mg/kg) and oral lenalidomide (25 mg/day) for up to 12 cycles (28 days each), followed by tafasitamab monotherapy (in patients with stable disease or better) until disease progression. The primary endpoint was the proportion of patients with an objective response (centrally assessed), defined as a complete or partial response according to the 2007 International Working Group response criteria for malignant lymphoma. Antitumour activity analyses are based on all patients who received at least one dose of both tafasitamab and lenalidomide; safety analyses are based on all patients who received at least one dose of either study medication. Recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov, NCT02399085. FINDINGS: Between Jan 18, 2016, and Nov 15, 2017, 156 patients were screened: 81 were enrolled and received at least one dose of either study medication, and 80 received at least one dose of both tafasitamab and lenalidomide. Median follow-up was 13·2 months (IQR 7·3-20·4) as of data cutoff on Nov 30, 2018. 48 (60%; 95% CI 48-71) of 80 patients who received tafasitamab plus lenalidomide had an objective response: 34 (43%; 32-54) had a complete response and 14 (18%; 10-28) had a partial response. The most common treatment-emergent adverse events of grade 3 or worse were neutropenia (39 [48%] of 81 patients), thrombocytopenia (14 [17%]), and febrile neutropenia (ten [12%]). Serious adverse events occurred in 41 (51%) of 81 patients. The most frequently reported serious adverse events (in two or more patients) were pneumonia (five [6%]), febrile neutropenia (five [6%]), pulmonary embolism (three [4%]), bronchitis (two [2%]), atrial fibrillation (two [2%]), and congestive cardiac failure (two [2%]). INTERPRETATION: Tafasitamab in combination with lenalidomide was well tolerated and resulted in a high proportion of patients with relapsed or refractory diffuse large B-cell lymphoma ineligible for autologous stem-cell transplantation having a complete response, and might represent a new therapeutic option in this setting. FUNDING: MorphoSys.

1st Department of Internal Medicine Semmelweis University Budapest Hungary

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 Institut Catalá d'Oncologia Hospital Duran i Reynals Institut d'Investigacio Biomedica de Bellvitge Barcelona Spain

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

Department of Medicine 3 University Hospital Groβhadern Ludwig Maximilians University Munich Germany

Division of Hematology Department of Translational Medicine Università del Piemonte Orientale Amedeo Avogadro Novara Italy

Hématologie Hospices Civils de Lyon and Université de Lyon Lyon France

Maria Skłodowska Curie National 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 UK

MorphoSys Planegg Germany

Service d'Hématologie Clinique et de Thérapie Cellulaire Centres Hospitalier Universitaire Estaing Clermont Ferrand France

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

Comment In

Lancet Oncol. 2020 Jul;21(7):870-872. doi: 10.1016/S1470-2045(20)30275-8. PubMed

References provided by Crossref.org

Large B-cell lymphoma (LBCL): EHA Clinical Practice Guidelines for diagnosis, treatment, and follow-up

Safety and efficacy of tafasitamab with or without lenalidomide added to first-line R-CHOP for DLBCL: the phase 1b First-MIND study

Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma

Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options

The EHA Research Roadmap: Malignant Lymphoid Diseases

Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

Current Immunotherapy Approaches in Non-Hodgkin Lymphomas

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ClinicalTrials.gov
NCT02399085