For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20-based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the "cold" anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

Beatson West of Scotland Cancer Centre Glasgow United Kingdom

Bristol Cancer Institute Bristol United Kingdom

Department of Diagnostic Physics and

Department of Hemato Oncology Faculty of Medicine and Dentistry Palacky University and University Hospital Olomouc Czech Republic

Department of Hematooncology University Hospital Ostrava and Faculty of Medicine Ostrava University Ostrava Czech Republic

Department of Medical Biochemistry Oslo University Hospital Radiumhospitalet Oslo Norway

Department of Nuclear Medicine Oslo University Hospital Radiumhospitalet Oslo Norway

Department of Oncology Oslo University Hospital Radiumhospitalet Oslo Norway

Department of Pathology Oslo University Hospital Radiumhospitalet Oslo Norway

Department of Radiology and Nuclear Medicine

Dorset Cancer Centre Poole United Kingdom

Maria Sklodowska Curie National Institute of Oncology Kraków Poland

Nordic Nanovector ASA Oslo Norway

St Olav's Hospital and Department of Cancer Research and Molecular Medicine Norwegian University of Science and Technology Trondheim Norway

University of Manchester National Institutes of Health Research Manchester Biomedical Research Centre Christie Hospital Manchester United Kingdom

000      

00000naa a2200000 a 4500

001      

bmc21020141

003      

CZ-PrNML

005      

20210830101743.0

007      

ta

008      

210728s2020 xxu f 000 0|eng||

009      

AR

024    7_

$a 10.1182/bloodadvances.2020002583 $2 doi

035    __

$a (PubMed)32877524

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a xxu

100    1_

$a Kolstad, Arne $u Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

245    10

$a Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma / $c A. Kolstad, T. Illidge, N. Bolstad, S. Spetalen, U. Madsbu, C. Stokke, J. Blakkisrud, A. Løndalen, N. O'Rourke, M. Beasley, W. Jurczak, UM. Fagerli, M. Kaščák, M. Bayne, A. Obr, J. Dahle, L. Rojkjaer, V. Pascal, H. Holte

520    9_

$a For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20-based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the "cold" anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

650    _2

$a monoklonální protilátky $x terapeutické užití $7 D000911

650    _2

$a lidé $7 D006801

650    12

$a imunokonjugáty $7 D018796

650    12

$a nehodgkinský lymfom $x farmakoterapie $x radioterapie $7 D008228

650    _2

$a kvalita života $7 D011788

650    _2

$a rituximab $7 D000069283

655    _2

$a klinické zkoušky, fáze I $7 D017426

655    _2

$a časopisecké články $7 D016428

655    _2

$a práce podpořená grantem $7 D013485

700    1_

$a Illidge, Tim $u University of Manchester, National Institutes of Health Research Manchester Biomedical Research Centre, Christie Hospital, Manchester, United Kingdom

700    1_

$a Bolstad, Nils $u Department of Medical Biochemistry, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

700    1_

$a Spetalen, Signe $u Department of Pathology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

700    1_

$a Madsbu, Ulf $u Department of Radiology and Nuclear Medicine

700    1_

$a Stokke, Caroline $u Department of Diagnostic Physics, and

700    1_

$a Blakkisrud, Johan $u Department of Diagnostic Physics, and

700    1_

$a Løndalen, Ayca $u Department of Nuclear Medicine, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

700    1_

$a O'Rourke, Noelle $u Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom

700    1_

$a Beasley, Matthew $u Bristol Cancer Institute, Bristol, United Kingdom

700    1_

$a Jurczak, Wojciech $u Maria Sklodowska-Curie National Institute of Oncology, Kraków, Poland

700    1_

$a Fagerli, Unn-Merete $u St. Olav's Hospital and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

700    1_

$a Kaščák, Michal $u Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, Ostrava University, Ostrava, Czech Republic

700    1_

$a Bayne, Mike $u Dorset Cancer Centre, Poole, United Kingdom

700    1_

$a Obr, Aleš $u Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic; and

700    1_

$a Dahle, Jostein $u Nordic Nanovector ASA, Oslo, Norway

700    1_

$a Rojkjaer, Lisa $u Nordic Nanovector ASA, Oslo, Norway

700    1_

$a Pascal, Veronique $u Nordic Nanovector ASA, Oslo, Norway

700    1_

$a Holte, Harald $u Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

773    0_

$w MED00194912 $t Blood advances $x 2473-9537 $g Roč. 4, č. 17 (2020), s. 4091-4101

856    41

$u https://pubmed.ncbi.nlm.nih.gov/32877524 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y p $z 0

990    __

$a 20210728 $b ABA008

991    __

$a 20210830101743 $b ABA008

999    __

$a ok $b bmc $g 1690847 $s 1140587

BAS    __

$a 3

BAS    __

$a PreBMC

BMC    __

$a 2020 $b 4 $c 17 $d 4091-4101 $e 20200908 $i 2473-9537 $m Blood advances $n Blood Adv $x MED00194912

LZP    __

$a Pubmed-20210728