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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
Ajay Nooka1, Charise Gleason, Daniela Casbourne
1Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA, USA.
Abstract:
Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit β5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route is associated with a lower incidence of grade 3/4 peripheral neuropathy, it remains a major concern. The second generation proteasome inhibitors are promising, with increased preclinical efficacy and a better administration schedule. The current review spotlights the second generation proteasome inhibitors with special focus on the safety and efficacy of carfilzomib, an epoxyketone with lesser peripheral neuropathy, which exhibits irreversible proteasome inhibition. In this article, we review the pharmacology and preclinical and clinical efficacy and safety of carfilzomib alone and in combination with other chemotherapeutic agents in the various lymphoid neoplasms and multiple myeloma as well as ongoing clinical trials.
Insights
Second-generation proteasome inhibitors like carfilzomib offer improved efficacy and safety for multiple myeloma treatment. This review highlights carfilzomib
Area of Science:
- Oncology
- Pharmacology
Background:
- Proteasome inhibitors, such as bortezomib, have transformed multiple myeloma therapy.
- Acquired resistance and peripheral neuropathy are significant challenges with bortezomib treatment.
- Second-generation proteasome inhibitors demonstrate enhanced preclinical efficacy and improved administration.
Purpose of the Study:
- To review the safety and efficacy of second-generation proteasome inhibitors.
- To spotlight carfilzomib, focusing on its pharmacology and clinical outcomes.
- To evaluate carfilzomib's role in lymphoid neoplasms and multiple myeloma.
Main Methods:
- Review of preclinical and clinical data on carfilzomib.
- Analysis of carfilzomib's efficacy and safety profile, alone and in combination therapies.
- Examination of ongoing clinical trials involving carfilzomib.
Main Results:
- Carfilzomib, an irreversible proteasome inhibitor, shows promise with reduced peripheral neuropathy.
- Preclinical studies indicate increased efficacy compared to first-generation inhibitors.
- Clinical data suggests favorable safety and efficacy in multiple myeloma and lymphoid neoplasms.
Conclusions:
- Carfilzomib represents a significant advancement in proteasome inhibitor therapy for multiple myeloma.
- Its improved safety profile, particularly regarding peripheral neuropathy, is a key advantage.
- Further clinical trials are essential to fully establish carfilzomib's therapeutic potential.
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