The role of carfilzomib in relapsed/refractory multiple myeloma:
Andrew Yee
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TLDR
Carfilzomib as discussed by the authors is the second proteasome inhibitor approved for relapsed multiple myeloma and has been an active and versatile drug, based on its efficacy as a single agent; superiority as a doublet with dexamethasone compared with bortezomib and dexamethylamine; and as a partner in diverse three drug combinations such as with lenalidomide or daratumumab.Abstract:
Carfilzomib is the second proteasome inhibitor approved for relapsed multiple myeloma. Since its approval in 2012, carfilzomib has been an active and versatile drug, based on its efficacy as a single agent; superiority as a doublet with dexamethasone compared with bortezomib and dexamethasone; and as a partner in diverse three drug combinations such as with lenalidomide or daratumumab. While it has an established place in relapsed disease, clinicians should be aware of its cardiovascular and renal adverse event profile, which is manageable, in order to optimize outcomes. This review will provide a perspective on the current and future role of carfilzomib in relapsed/refractory multiple myeloma.read more
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26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and Therapy.
Andres J. Rubio,Alfonso E. Bencomo-Alvarez,James E Young,Vanessa V Velazquez,Joshua J. Lara,Mayra A. Gonzalez,Anna M. Eiring +6 more
TL;DR: In this article, the authors analyzed PSMD1 and PSMD3 mRNA and protein expression in cancerous tissue versus normal controls using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), comparing expression with overall survival.
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Daratumumab May Attenuate Cardiac Dysfunction Related to Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma: A Prospective Study.
Evangelos Terpos,Kimon Stamatelopoulos,Nikolaos Makris,Georgios Georgiopoulos,Ioannis Ntanasis-Stathopoulos,Maria Gavriatopoulou,Ageliki Laina,Evangelos Eleutherakis-Papaiakovou,Despina Fotiou,Nikolaos Kanellias,Panagiotis Malandrakis,D Delialis,Ioanna Andreadou,Efstathios Kastritis,Meletios A. Dimopoulos +14 more
TL;DR: In this article, the authors evaluated 25 patients with relapsed/refractory multiple myeloma (RRMM) who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) or Kd (n = 11).
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Hypertension, smoking, and preexistence of multiple cardiac risk factors correlate with carfilzomib-induced cardiovascular adverse events in a racially diverse population
Stacey Doran,Manu Mysore,Seyed Ebrahim Kassaian,E. Kotloff,Farin Kamangar,Ashkan Emadi,Jummai Apata,Brian Barr +7 more
TL;DR: In this paper , the authors conducted a single center retrospective study to identify risk factors for carfilzomib-associated cardiovascular events in a diverse, single-center population and found that patients with history of hypertension had a higher risk of cardiovascular adverse events.
Journal ArticleDOI
Patients with Very High Risk of Cardiovascular Adverse Events during Carfilzomib Therapy: Prevention and Management of Events in a Single Center Experience
Giulia Mingrone,Anna Astarita,Anna Colomba,Cinzia Catarinella,Marco Cesareo,Lorenzo Airale,Arianna Paladino,Dario Leone,Fabrizio Vallelonga,Sara Bringhen,Francesca Gay,Franco Veglio,Alberto Milan +12 more
TL;DR: In this paper , a novel approach with inducible ischemia imaging tests for patients at high baseline CV risk to rule out clinical conditions that could contraindicate the starting of Carfilzomib (CFZ) was proposed.
References
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Journal ArticleDOI
Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma
TL;DR: In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk–benefit profile.
Journal ArticleDOI
Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells.
Esther A. Obeng,Louise M. Carlson,Delia Gutman,William J. Harrington,Kelvin P. Lee,Lawrence H. Boise +5 more
TL;DR: It is found that MM cells have a lower threshold for PI-induced UPR induction and ER stress-induced apoptosis because they constitutively express ER stress survival factors to function as secretory cells.
Journal ArticleDOI
Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity
TL;DR: In this article, the authors used biotinylated-epoxomicin as a molecular probe and showed that it covalently binds to the LMP7, X, MECL1, and Z catalytic subunits of the proteasome.
Journal ArticleDOI
Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study
Philippe Moreau,Halyna Pylypenko,Sebastian Grosicki,Ievgenii Karamanesht,Xavier Leleu,Maria Grishunina,Grigoriy B Rekhtman,Zvenyslava Masliak,Tadeusz Robak,Anna V Shubina,Bertrand Arnulf,Martin Kropff,James Cavet,Dixie-Lee Esseltine,Huaibao Feng,Suzette Girgis,Helgi van de Velde,William Deraedt,Jean-Luc Harousseau +18 more
TL;DR: The primary objective was to show non-inferiority of subcutaneous versus intravenous bortezomib in terms of overall response rate (ORR) after four cycles in patients with a diagnosis of measurable, secretory multiple myeloma who received one or more dose of drug.
Journal ArticleDOI
Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma
Deborah J. Kuhn,Qing Chen,Peter M. Voorhees,John S. Strader,Kevin D. Shenk,Congcong M. Sun,Susan Demo,Mark K. Bennett,Fijs W. B. van Leeuwen,Asher A. Chanan-Khan,Robert Z. Orlowski +10 more
TL;DR: A novel, irreversible, epoxomicin-related proteasome inhibitor, carfilzomib, showed increased efficacy and was active against bortezomib-resistant MM cell lines and samples from patients with clinical bortazomib resistance, and acted synergistically with dexamethasone to enhance cell death.