Literature DB >> 26331915

'Real-life' experience of preapproval carfilzomib-based therapy in myeloma - analysis of cardiac toxicity and predisposing factors.

Sophia Danhof1, Martin Schreder1, Leo Rasche1, Susanne Strifler1, Hermann Einsele1, Stefan Knop1.   

Abstract

BACKGROUND: Carfilzomib, the second-generation proteasome inhibitor, is still awaiting approval for the treatment of multiple myeloma in Europe. Results from clinical trials have demonstrated favorable efficacy in advanced disease but have opened an ongoing debate on cardiac complications related to carfilzomib treatment. 'Real-life' data are scarce. METHODS/PATIENTS: At our institution, 22 patients were registered within the European Carfilzomib Access Program for treatment with carfilzomib, dexamethasone, and a third combination partner depending on patient characteristics and prior treatment. Patients had received a median of six previous lines of therapy, and most were refractory to bortezomib (77%) and immunomodulatory drugs (95%).
RESULTS: Overall response rate was 65% with a median progression-free survival of 6.0 months and a median duration of response of 6.8 months. Median overall survival was 14.9 months. Grade 3/4 adverse events (AEs) occurred in 50% of patients with 23% experiencing left ventricular failure. The risk of cardiac AEs was markedly increased after previous radiotherapy of the thoracic spine and concomitant administration of doxorubicin.
CONCLUSION: Carfilzomib-based treatment is efficient in advanced multiple myeloma. In our 'real-life' patients, we found considerable cardiotoxic effects in some cases, indicating a need for careful patient selection and close monitoring of the at-risk population.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Entities:  

Keywords:  cardiac toxicity; carfilzomib; doxorubicin; heavily pretreated patients; multiple myeloma; proteasome inhibition; radiotherapy

Mesh:

Substances:

Year:  2015        PMID: 26331915     DOI: 10.1111/ejh.12677

Source DB:  PubMed          Journal:  Eur J Haematol        ISSN: 0902-4441            Impact factor:   2.997


  23 in total

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2.  Predictive biomarkers and practical considerations in the management of carfilzomib-associated cardiotoxicity.

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Journal:  Leuk Lymphoma       Date:  2018-01-08

Review 3.  Cardiovascular Complications Associated with Multiple Myeloma Therapies: Incidence, Pathophysiology, and Management.

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4.  Cardiac and renal complications of carfilzomib in patients with multiple myeloma.

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8.  Evaluation of Cardiovascular Toxicity Associated with Treatments Containing Proteasome Inhibitors in Multiple Myeloma Therapy.

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Review 10.  Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials.

Authors:  Ajai Chari; A Keith Stewart; Stuart D Russell; Philippe Moreau; Joerg Herrmann; Jose Banchs; Roman Hajek; John Groarke; Alexander R Lyon; George N Batty; Sunhee Ro; Mei Huang; Karim S Iskander; Daniel Lenihan
Journal:  Blood Adv       Date:  2018-07-10
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