A practical review on carfilzomib in multiple myeloma

Muchtar, Eli; Gertz, Morie A.; Magen, Hila

doi:10.1111/ejh.12749

Cited by 52 publications

(65 citation statements)

References 52 publications

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“…1,2 The accelerated approval of carfilzomib in July 2012 was based on the promising results of a single-arm multicenter trial enrolling 266 patients with recurrent and/or refractory multiple myeloma. The next-generation proteasome inhibitor carfilzomib is reported to increase the frequency and depth of responses, and improves survival in heavily pretreated patients with multiple myeloma.…”

Section: Introductionmentioning

confidence: 99%

Measuring cardiopulmonary complications of carfilzomib treatment and associated risk factors using the SEER‐Medicare database

Fakhri

Fiala

Shah

et al. 2019

Cancer

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BACKGROUND: Carfilzomib improves survival in patients with recurrent myeloma. Given the strict eligibility criteria in clinical trials, the actual frequency of cardiac adverse events (CAEs) and pulmonary adverse events (PAEs) and the risk factors associated with these AEs in the general population need to be established. METHODS: The authors extracted myeloma cases in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000 through 2013 and corresponding claims through 2014. They then identified patients who received carfilzomib during their disease course. Subsequently, the International Classification of Diseases, Ninth Revision (ICD-9) was used to identify all the codes for CAEs, PAEs, and respiratory infections associated with carfilzomib use. Preexisting diagnoses corresponding to the CAEs and PAEs of interest were excluded to distinguish toxicity from comorbidity. Multivariate Cox regression was performed to determine those variables independently associated with the development of CAEs and PAEs. RESULTS: Of the 635 patients analyzed, the median age was 72 years (range, 36-94 years); 55% of the patients were male and 79% were white. The median duration of carfilzomib treatment was 58 days (range, 1-716 days). Overall, approximately 66% of the patients had codes for either CAEs or PAEs. In terms of CAEs, approximately 22% of patients developed hypertension, 15% developed peripheral edema, and 14% experienced heart failure. With regard to PAEs, approximately 28% of patients developed dyspnea, 15% developed cough, and 15% developed pneumonia. Only chronic obstructive pulmonary disease (COPD) was found to be independently associated with the development of CAEs. Patients with preexisting COPD were found to have a 40% increase in their hazard of developing CAEs (adjusted hazard ratio, 1.40; 95% CI, 1.03-1.90). CONCLUSIONS: In older adults with myeloma who are undergoing treatment with carfilzomib, new cardiac and pulmonary diagnoses were common. Patients with preexisting COPD were found to be at an increased risk of developing CAEs. Cancer 2020;126:808-813.

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Section: Introductionmentioning

confidence: 99%

Measuring cardiopulmonary complications of carfilzomib treatment and associated risk factors using the SEER‐Medicare database

Fakhri

Fiala

Shah

et al. 2019

Cancer

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“…The inhibition reaction has a barrier of about 7 kcal/mol. For X=Cl and Br (2,4) we computed barriers of about 12 and 13 kcal/mol and reaction energies of -11 and -10 kcal/mol. 15 The reactions of irreversible inhibitors were computed to be more exothermic than -22 kcal/mol.…”

Section: Introductionmentioning

confidence: 99%

Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors

et al. 2016

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We propose a structure-based protocol for the development of customized covalent inhibitors. Starting from a known inhibitor, in the first and second steps appropriate substituents of the warhead are selected on the basis of quantum mechanical (QM) computations and hybrid approaches combining QM with molecular mechanics (QM/MM). In the third step the recognition unit is optimized using docking approaches for the noncovalent complex. These predictions are finally verified by QM/MM or molecular dynamic simulations. The applicability of our approach is successfully demonstrated by the design of reversible covalent vinylsulfone-based inhibitors for rhodesain. The examples show that our approach is sufficiently accurate to identify compounds with the desired properties but also to exclude nonpromising ones.

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“…34 Carfilzomib is an irreversible 20S proteasome inhibitor which causes inhibition of tumor growth and apoptosis. 34 Carfilzomib is an irreversible 20S proteasome inhibitor which causes inhibition of tumor growth and apoptosis.…”

Section: How S Hould Patients Underg O De S En S Itiz Ati On?mentioning

confidence: 99%

Desensitization in heart transplant recipients: Who, when, and how

Shah

Patel

2019

Clinical Transplantation

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The number of heart transplant candidates who have pre-formed antibodies against human leukocyte antigens (HLAs) is increasing over time. The purpose of this review is to discuss the process of antibody desensitization for heart transplant candidates. Specifically, we review the current status of antibody detection including identification, strength, and potential pathogenicity. We discuss which patients and when should they undergo desensitization therapies during heart transplant evaluation. Specific therapies including mechanical removal of antibodies, intravenous immunoglobulins, and novel immunosuppressive agents targeting antibody production will be discussed. Finally, future research strategies to develop novel desensitization therapies for heart transplant candidates will be reviewed. K E Y W O R D Sdesensitization, heart disease, sensitization

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A practical review on carfilzomib in multiple myeloma

Cited by 52 publications

References 52 publications

Measuring cardiopulmonary complications of carfilzomib treatment and associated risk factors using the SEER‐Medicare database

Measuring cardiopulmonary complications of carfilzomib treatment and associated risk factors using the SEER‐Medicare database

Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors

Desensitization in heart transplant recipients: Who, when, and how

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