Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F20%3A73603608" target="_blank" >RIV/61989592:15110/20:73603608 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.sciencedirect.com/science/article/pii/S1470204520302254?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1470204520302254?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/S1470-2045(20)30225-4" target="_blank" >10.1016/S1470-2045(20)30225-4</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study
Popis výsledku v původním jazyce
Background Patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for autologous stemcell 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 highdose 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. Copyright (C) 2020 Elsevier Ltd. All rights reserved.
Název v anglickém jazyce
Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study
Popis výsledku anglicky
Background Patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for autologous stemcell 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 highdose 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. Copyright (C) 2020 Elsevier Ltd. All rights reserved.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30205 - Hematology
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
The Lancet Oncology
ISSN
1470-2045
e-ISSN
—
Svazek periodika
21
Číslo periodika v rámci svazku
7
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
11
Strana od-do
978-988
Kód UT WoS článku
000545328900035
EID výsledku v databázi Scopus
2-s2.0-85086663162