Enzymatic activities of circulating plasma proteasomes in newly diagnosed multiple myeloma patients treated with carfilzomib, lenalidomide and dexamethasone Journal Article


Authors: Manasanch, E. E.; Fernández de Larrea, C.; Zingone, A.; Steinberg, S. M.; Kwok, M.; Tageja, N.; Bhutani, M.; Kazandjian, D.; Roschewski, M.; Wu, P.; Carter, G.; Zuchlinski, D.; Mulquin, M.; Lamping, L.; Costello, R.; Burton, D.; Gil, L. A.; Figg, W. D.; Maric, I.; Calvo, K. R.; Yuan, C.; Stetler-Stevenson, M.; Korde, N.; Landgren, O.
Article Title: Enzymatic activities of circulating plasma proteasomes in newly diagnosed multiple myeloma patients treated with carfilzomib, lenalidomide and dexamethasone
Abstract: The proteasome inhibitor carfilzomib is highly effective in the treatment of multiple myeloma. It irreversibly binds the chymotrypsin-like active site in the β5 subunit of the 20S proteasome. Despite impressive response rates when carfilzomib is used in combination with immunomodulatory agents in newly diagnosed multiple myeloma patients; no biomarker exists to accurately predict response and clinical outcomes. We prospectively assessed the activity in peripheral blood of the chymotrypsin-like (CHYM), caspase-like (CASP) and trypsin-like (TRYP) proteolytic sites in 45 newly diagnosed multiple myeloma patients treated with eight cycles of carfilzomib, lenalidomide and dexamethasone (CRd) (NCT01402284). Samples were collected per protocol and proteasome activity measured through a fluorogenic assay. Median CHYM levels after one dose of carfilzomib decreased by >70%. CHYM and CASP activity decreased throughout treatment reaching a minimum after eight cycles of treatment. Higher levels of proteasome activity associated with higher disease burden (r > 0.30; p < 0.05) and higher disease stage (0.10 < p <0.20). No association was found with the probability of achieving a complete response, minimal residual disease negativity or time to best response. Further studies evaluating proteasome activity in malignant plasma cells may help elucidate how proteasome activity can be used as a biomarker in multiple myeloma. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Keywords: proteasome; biomarker; myeloma; activity
Journal Title: Leukemia and Lymphoma
Volume: 58
Issue: 3
ISSN: 1042-8194
Publisher: Taylor & Francis Group  
Date Published: 2017-01-01
Start Page: 639
End Page: 645
Language: English
DOI: 10.1080/10428194.2016.1214953
PROVIDER: scopus
PUBMED: 27687480
DOI/URL:
Notes: Article -- Export Date: 2 February 2017 -- Source: Scopus
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MSK Authors
  1. Carl Ola Landgren
    188 Landgren
  2. Neha Sanat Korde
    62 Korde