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


CONCLUSIONS
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.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany.
Sophia
S
Danhof
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany.
Martin
M
Schreder
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany.
Leo
L
Rasche
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany.
Susanne
S
Strifler
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany.
Hermann
H
Einsele
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany.
Stefan
S
Knop
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D066126:Cardiotoxicity; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004198:Disease Susceptibility; D017277:Drug Approval; D019008:Drug Resistance, Neoplasm; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D009842:Oligopeptides; D061988:Proteasome Inhibitors; C524865:carfilzomib
cardiac toxicity; carfilzomib; doxorubicin; heavily pretreated patients; multiple myeloma; proteasome inhibition; radiotherapy