Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II
Hematology Disease Topics & Pathways:
Polatuzumab vedotin is an ADC composed of a humanized anti-CD79b monoclonal antibody conjugated to monomethyl auristatin E (vcMMAE) and it is approved by the FDA for treatment of r/r DLBCL when used in combination with bendamustine and rituximab.
Here, we investigated the in vitro and in vivo anti-tumor activity of loncastuximab tesirine combined with polatuzumab vedotin in pre-clinical models of non-Hodgkin lymphoma (NHL).
In vitro, the combination of loncastuximab tesirine and polatuzumab vedotin was tested in three human-derived, CD19 and CD79b-positive NHL cell lines (WSU-DLCL2, TMD8 and Ramos) and it resulted in synergistic (TMD8 and Ramos) and additive (WSU-DLCL2) activity, as assessed by the Chou-Talalay method.
Quantification of cell viability (propidium iodide [PI]-negative and Annexin V-negative) and early/late apoptosis (Annexin V-positive and PI-negative/ Annexin V-positive and-PI positive) on TMD8 and Ramos cells treated with loncastuximab tesirine, polatuzumab vedotin or the combination of the two agents showed a significant reduction of viable cells accompanied by an increase in apoptotic cells in the combination setting compared to the single agents.
In vivo, loncastuximab tesirine was tested either alone (0.25 or 0.5 mg/kg, single dose) or in combination with polatuzumab vedotin (1 mg/kg, single dose) in the WSU-DLCL2 xenograft model. At the highest dose of loncastuximab tesirine, combination with polatuzumab vedotin resulted in improved anti-tumor activity and superior response rate compared to the 2 agents in monotherapy. All treatment regimens were well tolerated by the mice, as assessed by body weight measurements and frequent observation for signs of treatment-related side effects.
In conclusion, the combination of loncastuximab tesirine and polatuzumab vedotin resulted in improved anti-tumor activity both in vitro and in vivo in lymphoma preclinical models and it was well tolerated. Altogether, these novel pre-clinical data warrant translation of the combination of loncastuximab tesirine and polatuzumab vedotin into the clinic for the treatment of NHL.
Disclosures: Sachini: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Jabeen: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. van Berkel: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Zammarchi: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties.
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