PMID- 32877524 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20220531 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 4 IP - 17 DP - 2020 Sep 8 TI - Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma. PG - 4091-4101 LID - 10.1182/bloodadvances.2020002583 [doi] AB - 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. CI - (c) 2020 by The American Society of Hematology. FAU - Kolstad, Arne AU - Kolstad A AD - Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. FAU - Illidge, Tim AU - Illidge T AD - University of Manchester, National Institutes of Health Research Manchester Biomedical Research Centre, Christie Hospital, Manchester, United Kingdom. FAU - Bolstad, Nils AU - Bolstad N AD - Department of Medical Biochemistry, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. FAU - Spetalen, Signe AU - Spetalen S AD - Department of Pathology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. FAU - Madsbu, Ulf AU - Madsbu U AD - Department of Radiology and Nuclear Medicine. FAU - Stokke, Caroline AU - Stokke C AD - Department of Diagnostic Physics, and. FAU - Blakkisrud, Johan AU - Blakkisrud J AD - Department of Diagnostic Physics, and. FAU - Londalen, Ayca AU - Londalen A AD - Department of Nuclear Medicine, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. FAU - O'Rourke, Noelle AU - O'Rourke N AD - Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. FAU - Beasley, Matthew AU - Beasley M AD - Bristol Cancer Institute, Bristol, United Kingdom. FAU - Jurczak, Wojciech AU - Jurczak W AD - Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland. FAU - Fagerli, Unn-Merete AU - Fagerli UM AD - St. Olav's Hospital and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. FAU - Kascak, Michal AU - Kascak M AD - Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, Ostrava University, Ostrava, Czech Republic. FAU - Bayne, Mike AU - Bayne M AD - Dorset Cancer Centre, Poole, United Kingdom. FAU - Obr, Ales AU - Obr A AD - Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic; and. FAU - Dahle, Jostein AU - Dahle J AD - Nordic Nanovector ASA, Oslo, Norway. FAU - Rojkjaer, Lisa AU - Rojkjaer L AD - Nordic Nanovector ASA, Oslo, Norway. FAU - Pascal, Veronique AU - Pascal V AD - Nordic Nanovector ASA, Oslo, Norway. FAU - Holte, Harald AU - Holte H AD - Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. LA - eng SI - ClinicalTrials.gov/NCT01796171 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (Antibodies, Monoclonal) RN - 0 (Immunoconjugates) RN - 4F4X42SYQ6 (Rituximab) SB - IM MH - Antibodies, Monoclonal/therapeutic use MH - Humans MH - *Immunoconjugates MH - *Lymphoma, Non-Hodgkin/drug therapy/radiotherapy MH - Quality of Life MH - Rituximab PMC - PMC7479948 COIS- Conflict-of-interest disclosure: A.K. declares advisory board participation for Nordic Nanovector ASA. T.I. declares advisory board participation for Nordic Nanovector ASA, Roche, and Takeda. S.S. declares lecture honoraria from Novartis and Sanofi Genzyme. W.J. declares research funding/grants from Nordic Nanovector ASA. U.-M.F. declares advisory board participation for Takeda and Roche. H.H. declares advisory board participation for Nordic Nanovector ASA, Novartis, Roche, Gilead, and Takeda and lecture honoraria from Novartis. J.D. and V.P. are employees of Nordic Nanovector ASA and owners of performance share units. J.D. also declares ownership of shares. L.R. was an employee of Nordic Nanovector ASA at the time of this study. The remaining authors declare no competing financial interests. EDAT- 2020/09/03 06:00 MHDA- 2021/05/15 06:00 PMCR- 2020/09/02 CRDT- 2020/09/03 06:00 PHST- 2020/06/05 00:00 [received] PHST- 2020/07/29 00:00 [accepted] PHST- 2020/09/03 06:00 [entrez] PHST- 2020/09/03 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/09/02 00:00 [pmc-release] AID - S2473-9529(20)31172-1 [pii] AID - 2020/ADV2020002583 [pii] AID - 10.1182/bloodadvances.2020002583 [doi] PST - ppublish SO - Blood Adv. 2020 Sep 8;4(17):4091-4101. doi: 10.1182/bloodadvances.2020002583.