TY  - JOUR
A1  - San-Miguel, Jesus F.
A1  - Einsele, Hermann
A1  - Moreau, Philippe
T1  - The Role of Panobinostat Plus Bortezomib and Dexamethasone in Treating Relapsed or Relapsed and Refractory Multiple Myeloma: A European Perspective
JF  - Advances in Therapy
N2  - Panobinostat is an oral pan-histone deacetylase inhibitor developed by Novartis. Panobinostat acts via epigenetic modification and inhibition of the aggresome pathway. In August 2015, the European Commission authorized panobinostat for use in combination with bortezomib and dexamethasone for the treatment of relapsed or relapsed and refractory multiple myeloma (MM) in patients who have received aeyen2 prior regimens including bortezomib and an immunomodulatory drug. In January 2016, the National Institute for Health and Care Excellence recommended panobinostat for use in the same combination and patient population. The authorization and recommendation were based on results from the pivotal phase 3 PANORAMA 1 (NCT01023308) clinical trial, which demonstrated an improvement in median progression-free survival of 7.8 months for the three-drug combination compared with placebo plus bortezomib and dexamethasone in this patient population. This review will discuss the current treatment landscape for relapsed/refractory MM, the mechanism of action of panobinostat, clinical data supporting the European authorization, concerns about safety and strategies for mitigating toxicity, and how panobinostat fits into the current MM landscape in Europe.
KW  - multiple myeloma
KW  - oncology
KW  - panobinostat
KW  - relapsed and refractory
KW  - daratumumab monotherapy
KW  - relapsed
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186840
VL  - 33
IS  - 11
ER  - 
TY  - JOUR
A1  - Dimopoulos, Meletios A.
A1  - Weisel, Katja C.
A1  - Song, Kevin W.
A1  - Delforge, Michel
A1  - Karlin, Lionel
A1  - Goldschmidt, Hartmut
A1  - Moreau, Philippe
A1  - Banos, Anne
A1  - Oriol, Albert
A1  - Garderet, Laurent
A1  - Cavo, Michele
A1  - Ivanova, Valentina
A1  - Alegre, Adrian
A1  - Martinez-Lopez, Joaquin
A1  - Chen, Christine
A1  - Spencer, Andrew
A1  - Knop, Stefan
A1  - Bahlis, Nizar J.
A1  - Renner, Christoph
A1  - Yu, Xin
A1  - Hong, Kevin
A1  - Sternas, Lars
A1  - Jacques, Christian
A1  - Zaki, Mohamed H.
A1  - San Miguel, Jesus F.
T1  - Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone
JF  - Haematologica
N2  - Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P < 0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or highdose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4; 14) (15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14).
KW  - translocation
KW  - plus dexamethasone
KW  - deletion 17P
KW  - bortezomib
KW  - therapy
KW  - abnormalities
KW  - stem-cell transplantation
KW  - growth-factor receptor 3
KW  - high-risk cytogenetics
KW  - intergroupe francophone
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140349
VL  - 100
IS  - 10
SP  - 1327
EP  - 1333
ER  -