Objectives: Carfilzomib is a new agent for the treatment of relapsed and refractory multiple myeloma (MM). This article presents a comprehensive overview of the pharmacokinetics, pharmacodynamics, dosing schedule, safety, efficacy, preparation and administration of carfilzomib, and its role in treating MM patients.
Key Findings: Carfilzomib is a selective proteasome inhibitor that differs structurally and mechanistically from bortezomib. In patients' whole-blood and peripheral-blood mononuclear cells, carfilzomib inhibited proteasomal and immunoproteasomal activity by 70-80%. Approved carfilzomib dosing is based on body surface area, and is given on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle (20 mg/m(2) in cycle 1; 27 mg/m(2) in cycle 2+). Premedication with dexamethasone and adequate hydration are recommended to reduce the risk of adverse events. The median t1/2 of carfilzomib is short (0.29-0.48 h), with no accumulation detected between doses. In clinical studies in relapsed and refractory MM. and in combinations in newly diagnosed MM, single-agent carfilzomib demonstrated significant durable activity, good tolerability and a favourable safety profile, supporting its extended use.
Conclusions: Carfilzomib represents an important addition to the treatment armamentarium for patients with relapsed and/or refractory MM, and studies are underway evaluating the role of single-agent carfilzomib in additional clinical settings as well as in different combinations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/jphp.12072 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Health-Related Quality of Life in Patients With Relapsed/Refractory Multiple Myeloma Treated With Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone: An Analysis of Patient-Reported Outcomes From the Phase 3 CANDOR Trial.
Clin Lymphoma Myeloma Leuk
February 2025
Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:
Background: In the phase 3 CANDOR trial (NCT03158688), daratumumab added to carfilzomib and dexamethasone (KdD) significantly prolonged progression-free survival relative to carfilzomib and dexamethasone (Kd) alone in previously treated patients with relapsed/refractory multiple myeloma (RRMM).
Materials And Methods: We present a post hoc analysis of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-item module (EORTC QLQ-C30) and EORTC QLQ Myeloma 20-item module (EORTC QLQ-MY20) patient-reported outcome (PRO) measures from the CANDOR trial.
Results: Median (range) duration of observation for PROs was 18.
How First-Line Therapy is Changing in Transplant-Eligible Multiple Myeloma Patients.
Mediterr J Hematol Infect Dis
March 2025
Hematology Unit, dept of Clinical and Experimental Medicine, University of Pisa Italy.
Multiple myeloma is a malignant haematological neoplasm characterised by the proliferation of plasma cells in the bone marrow. Each year, over 35,000 new cases are diagnosed in the United States, and nearly 13,000 patients die from the disease.1 The main cause of morbidity is bone disease, characterised by osteolytic lesions, which, unlike other malignancies that metastasise to bone, are not followed by new bone formation.
View Article and Find Full Text PDFSignificance of mouse xenograft tumor model using patient-derived cancer organoids for clinical drug development.
Front Oncol
February 2025
Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan.
Background: and preclinical examinations of cancer cell lines are performed to determine the effectiveness of new drugs before initiating clinical trials. However, there is often a significant disparity between the promising results observed in preclinical evaluations and actual outcomes in clinical trials. Therefore, we hypothesized that this inconsistency might be due to the differences between the characteristics of cell lines and actual cancers in patients.
View Article and Find Full Text PDFCarfilzomib inhibits the progression of hepatocellular cancer by upregulating GADD45α expression.
Oncol Lett
April 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Hepatocellular carcinoma (HCC) ranks among the most prevalent and lethal cancers affecting humans. Currently, there are limited effective treatments available for HCC. Carfilzomib, a proteasome inhibitor, is known to exert anti-HCC activities; however, its underlying mechanisms of action remain unclear.
View Article and Find Full Text PDFInhibitors of the ubiquitin‑proteasome system rescue cellular levels and ion transport function of pathogenic pendrin (SLC26A4) protein variants.
Int J Mol Med
May 2025
Institute of Pharmacology and Toxicology, Paracelsus Medical University, A-5020 Salzburg, Austria.
Pendrin (SLC26A4) is an anion exchanger abundantly expressed in the inner ear, kidney and thyroid, and its malfunction resulting from genetic mutation leads to Pendred syndrome and non‑syndromic deafness DFNB4. Pathogenic variants of the pendrin protein are less expressed than the wild‑type, but the mechanism underlying this phenomenon is unknown. In the present study, the hypothesis that reduced protein expression stems from increased protein degradation was explored.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!