Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu klinické zkoušky, fáze II, časopisecké články, multicentrická studie, práce podpořená grantem
PubMed
32511983
DOI
10.1016/s1470-2045(20)30225-4
PII: S1470-2045(20)30225-4
Knihovny.cz E-zdroje
- MeSH
- chemorezistence účinky léků MeSH
- difúzní velkobuněčný B-lymfom farmakoterapie patologie MeSH
- dospělí MeSH
- humanizované monoklonální protilátky aplikace a dávkování MeSH
- lenalidomid aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie patologie MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- následné studie MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- záchranná terapie * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- humanizované monoklonální protilátky MeSH
- lenalidomid MeSH
- tafasitamab MeSH Prohlížeč
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 Medicine 3 University Hospital Groβhadern Ludwig Maximilians University Munich Germany
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
Università degli Studi di Perugia Azienda Ospedaliera Santa Maria di Terni Terni Italy
Citace poskytuje Crossref.org
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Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas
ClinicalTrials.gov
NCT02399085