Adcetris
brentuximab vedotin · CD30Three xenograft models from human HL and ALCL cell lines
Blenrep: animal efficacy model or human cells?
belantamab mafodotin · BCMA
Efficacy evidence
Human MM xenografts (NCI-H929, OPM-2, MM1Sluc) and EL4-hBCMA syngeneic mouse model
“Belantamab mafodotin induced durable tumour growth regression in xenograft mice models bearing human multiple myeloma NCI-H929, OPM-2, and MM1Sluc cells, and dependently on the presence of CD8+ T-cells in immune-competent syngeneic mouse expressing human BCMA (EL4-hBCMA).”
Why that model
No binding to mouse or rat BCMA, so efficacy relied on human MM xenografts and human-BCMA-expressing mouse tumour
“Supporting the selection of cynomolgus monkey as a species for toxicological evaluation, comparable affinity to monkey BCMA (Kd 0.7 nM at 25°C and 8.4 nM at 37°C) was shown, and no binding to mouse or rat BCMA.”
Reviewer's view of the efficacy data
FDA: EL4-hBCMA syngeneic model limited; predictive value for human disease uncertain
“This model has several limitations in that it is a mouse lymphoma cell line expressing human BCMA and its predictive value for human disease is uncertain.”
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