Scientific publications
Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Scientific Publication
Maria-Victoria Mateos (1), Robert Z Orlowski (2), Enrique M Ocio (3), Paula Rodríguez-Otero (4), Donna Reece (5), Philippe Moreau (6), Nikhil Munshi (7), David E Avigan (8), David S Siegel (9), Razi Ghori (10), Mohammed Z H Farooqui (10), Patricia Marinello (10), Jesus San-Miguel (4)
Multiple myeloma (MM) is characterised by generalised immune suppression, partly mediated by loss of T‐cell repertoire, inhibition of antigen‐presenting cells and increased expression of the inhibitory programmed death 1 (PD‐1, also termed PDCD1) immune checkpoint pathway, (Neri et al , 2016).
PD‐1 up‐regulation on T cells is associated with disease relapse and resistance to chemotherapy (Tamura et al , 2013), and blockade may represent a promising treatment option.
However, single‐agent PD‐1 inhibition did not show significant tumour regression, suggesting that combination therapy may be necessary (Lesokhin et al , 2016). In pre‐clinical studies, lenalidomide, an immunomodulatory drug (IMiD), plus PD‐1/PD‐L1 (CD274) blockade enhanced MM cell death induced by PD‐1/PD‐L1 immune checkpoint blockade alone (Gorgun et al , 2015).
CITATION Br J Haematol. 2019 Sep;186(5):e117-e121. doi: 10.1111/bjh.15946. Epub 2019 May 15.
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