• Monika EngelhardtEmail author
  • Magdalena Szymaniak-Vits
  • Stefanie Ajayi
  • Sandra Maria Dold
  • Stefan Jürgen Müller
  • Sophia Scheubeck
  • Ralph Wäsch
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 212)


Carfilzomib (CFZ) is a potent, second-generation proteasome inhibitor (PI), with significant activity as a single agent and in combination with other antimyeloma agents in patients with relapsed or refractory multiple myeloma (RRMM). CFZ binds selectively and irreversibly to its target and leads to antiproliferative and proapoptotic effects on cancer cells. This irreversible inhibition is dose- and time-dependent in vitro and in vivo. CFZ as monotherapy and in combination with other antimyeloma agents (e.g., as CFZ and dexamethasone [Kd]) achieved very good responses, progression-free survival (PFS) and overall survival (OS). In several ongoing studies, CFZ is being investigated in triplet and quadruplet schedules of CFZ, lenalidomide and dexamethasone (KRd), CFZ, cyclophosphamide, dexamethasone (KCd) and with antibodies, like elotuzumab or daratumumab. The multitude of completed and ongoing studies confirmed a tolerable safety profile of CFZ, a significantly lower incidence of neuropathy compared to bortezomib (BTZ) and a slightly higher incidence of cardiotoxicity, which is closely observed and precautions taken to avoid them as best as possible. In July 2012, the US Food and Drug Administration (FDA) approved CFZ as a single agent for RRMM patients with disease progression after two prior therapies, including BTZ and immunomodulatory drugs (IMiDs). The combination of KRd and Kd followed, being approved by both FDA and European Medicines Agency (EMA) in 2015 and 2016, respectively. Moreover, CFZ is being evaluated in patients with newly diagnosed MM (NDMM), in high-risk smoldering MM and for maintenance approaches.


Novel proteasome inhibitor Irreversible Carfilzomib Relapsed/refractory disease Multiple myeloma 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Monika Engelhardt
    • 1
    • 2
    Email author
  • Magdalena Szymaniak-Vits
    • 1
  • Stefanie Ajayi
    • 1
    • 2
  • Sandra Maria Dold
    • 1
  • Stefan Jürgen Müller
    • 1
  • Sophia Scheubeck
    • 1
  • Ralph Wäsch
    • 1
  1. 1.Hematology and Oncology, Faculty of MedicineUniversity of FreiburgFreiburgGermany
  2. 2.Comprehensive Cancer Center Freiburg (CCCF)FreiburgGermany

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