Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

• Published in: Blood advances Vol. 4; no. 17; pp. 4091 - 4101
• Main Authors: Kolstad, Arne, Illidge, Tim, Bolstad, Nils, Spetalen, Signe, Madsbu, Ulf, Stokke, Caroline, Blakkisrud, Johan, Løndalen, Ayca, O'Rourke, Noelle, Beasley, Matthew, Jurczak, Wojciech, Fagerli, Unn-Merete, Kaščák, Michal, Bayne, Mike, Obr, Aleš, Dahle, Jostein, Rojkjaer, Lisa, Pascal, Veronique, Holte, Harald
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.09.2020; American Society of Hematology
• Subjects: Antibodies, Monoclonal - therapeutic use; Clinical Trials and Observations; Humans; Immunoconjugates; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - radiotherapy; Quality of Life; Rituximab
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020002583

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. •There is a high unmet need for new treatment options, particularly in elderly patients with relapsed/refractory FL.•Radioimmunotherapy is an underused option, and 177Lu-lilotomab satetraxetan may offer a safe and effective treatment for relapsed FL. [Display omitted]