Combination of 177 Lu-lilotomab with rituximab significantly improves the therapeutic outcome in preclinical models of non-Hodgkin's lymphoma

Abstract

Objectives: To investigate the therapeutic potential of the next-generation anti-CD37 radioimmunoconjugate ¹⁷⁷ Lu-lilotomab satetraxetan (¹⁷⁷ Lu-lilotomab) in combination with the anti-CD20 antibody rituximab for treatment of mice with non-Hodgkin's lymphoma (NHL) xenografts.

Methods: Nude mice with subcutaneous (s.c.) Burkitt's lymphoma Daudi xenografts and SCID mice intravenously (i.v.) injected with Mantle cell lymphoma Rec-1 cells were treated with either ¹⁷⁷ Lu-lilotomab or rituximab alone or with the combination of both treatments. Tumour volume, body weight, blood counts and clinical status were monitored. CD20 expression was measured using flow cytometry with fluorescence-labelled rituximab.

Results: The combination of ¹⁷⁷ Lu-lilotomab and rituximab was synergistic for treatment of nude mice with s.c. Daudi xenografts while it was additive for treatment of SCID mice with i.v. injected Rec-1 cells. Binding of rituximab to NHL cells in-vitro was increased by pretreatment with ¹⁷⁷ Lu-lilotomab.

Conclusions: Treatment of mice with NHL xenografts with ¹⁷⁷ Lu-lilotomab synergistically increased tumour suppression of subsequent anti-CD20 immunotherapy and improved survival. If the same effect is confirmed in a recently started clinical study, it could change the way radioimmunotherapy and CD20 immunotherapy would be used in the future.

Keywords: CD37; betalutin; lilotomab; lutetium; lymphoma; non-Hodgkin's; preclinical; radioimmunotherapy; rituximab; synergy.