Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies
David S. Siegel,Thomas Martin,Ajay K. Nooka,R. Donald Harvey,Ravi Vij,Ruben Niesvizky,Ashraf Badros,Sundar Jagannath,Leanne McCulloch,Kanya Rajangam,Sagar Lonial +10 more
TLDR
The data demonstrate that single-agent carfilzomib has an acceptable safety profile in heavily pre-treated patients with relapsed/refractory multiple myeloma, including those with pre-existing comorbidities.Abstract:
Carfilzomib, a selective proteasome inhibitor, was approved in 2012 for the treatment of relapsed and refractory multiple myeloma. Safety data for single-agent carfilzomib have been analyzed for 526 patients with advanced multiple myeloma who took part in one of 4 phase II studies (PX-171-003-A0, PX-171-003-A1, PX-171-004, and PX-171-005). Overall analyses of adverse events and treatment modifications are presented, as well as specific analyses of adverse events by organ system. Overall, the most common adverse events of any grade included fatigue (55.5%), anemia (46.8%), and nausea (44.9%). In the grouped analyses, any grade adverse events were reported in 22.1% for any cardiac (7.2% cardiac failure), 69.0% for any respiratory (42.2% dyspnea), and 33.1% for any grouped renal impairment adverse event (24.1% increased serum creatinine). The most common non-hematologic adverse events were generally Grade 1 or 2 in severity, while Grade 3/4 adverse events were primarily hematologic and mostly reversible. There was no evidence of cumulative bone marrow suppression, either neutropenia or thrombocytopenia, and febrile neutropenia occurred infrequently (1.1%). Notably, the incidence of peripheral neuropathy was low overall (13.9%), including patients with baseline peripheral neuropathy (12.7%). Additionally, the incidence of discontinuations or dose reductions attributable to adverse events was low. These data demonstrate that single-agent carfilzomib has an acceptable safety profile in heavily pre-treated patients with relapsed/refractory multiple myeloma. The tolerable safety profile allows for administration of full-dose carfilzomib, both for extended periods and in a wide spectrum of patients with advanced multiple myeloma, including those with pre-existing comorbidities.read more
Citations
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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.
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2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Paul A. Heidenreich,Biykem Bozkurt,David Aguilar,Larry A. Allen,Joni J. Byun,Monica Colvin,Anita Deswal,Mark H. Drazner,Shannon M. Dunlay,Linda R. Evers,James C. Fang,Savitri Fedson,Gregg C. Fonarow,Salim S. Hayek,Adrian F. Hernandez,Prateeti Khazanie,Michelle M. Kittleson,Christopher S. Lee,Mark S. Link,Carmelo A. Milano,Lorraine C. Nnacheta,Alexander T. Sandhu,Lynne W. Stevenson,Orly Vardeny,Amanda R. Vest,Clyde W. Yancy +25 more
TL;DR: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" as discussed by the authors provides patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.
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Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Philippe Moreau,Tamás Masszi,Norbert Grzasko,Nizar J. Bahlis,Markus Hansson,Ludek Pour,Irwindeep Sandhu,Peter Ganly,Bartrum W Baker,Sharon Jackson,Anne-Marie Stoppa,D. Simpson,Peter Gimsing,Antonio Palumbo,Laurent Garderet,Michele Cavo,Shaji Kumar,Cyrille Touzeau,Francis K. Buadi,Jacob P. Laubach,Deborah Berg,J. Lin,Alessandra Di Bacco,Ai Min Hui,Helgi van de Velde,Paul G. Richardson +25 more
TL;DR: The addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited.
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Proteasome inhibitors in cancer therapy
TL;DR: Investigation of the mechanisms of resistance is essential to further maximize the utility of this class of drugs in the era of personalized medicine.
Journal ArticleDOI
Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study
Meletios A. Dimopoulos,Philippe Moreau,Antonio Palumbo,Douglas E. Joshua,Ludek Pour,Roman Hájek,Thierry Facon,Heinz Ludwig,Albert Oriol,Hartmut Goldschmidt,Laura Rosiñol,Jan Straub,Aleksandr Suvorov,Carla Araujo,Elena Rimashevskaya,Tomas Pika,Gianluca Gaidano,Katja Weisel,Vesselina Goranova-Marinova,Anthony P. Schwarer,Leonard Minuk,Tamas Masszi,Ievgenii Karamanesht,Massimo Offidani,Vania Hungria,Andrew Spencer,Robert Z. Orlowski,Heidi H. Gillenwater,Nehal Mohamed,Shibao Feng,Wee Joo Chng +30 more
TL;DR: The primary endpoint was progression-free survival in the intention-to-treat population and carfilzomib with dexamethasone could be considered in patients with relapsed or refractory multiple myeloma.
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TL;DR: Lenalidomide plus dexamethasone is superior to placebo plus DexamethAsone in patients with relapsed or refractory multiple myeloma.
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