Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone

被引：63

作者：

Dimopoulos, Meletios A. ^{[1
]}

Weisel, Katja C. ^{[2
]}

Song, Kevin W. ^{[3
]}

Delforge, Michel ^{[4
]}

Karlin, Lionel ^{[5
]}

Goldschmidt, Hartmut ^{[6
,7
]}

Moreau, Philippe ^{[8
]}

Banos, Anne ^{[9
]}

Oriol, Albert ^{[10
]}

Garderet, Laurent ^{[11
]}

Cavo, Michele ^{[12
]}

Ivanova, Valentina ^{[13
]}

Alegre, Adrian ^{[14
]}

Martinez-Lopez, Joaquin ^{[15
]}

Chen, Christine ^{[16
]}

Spencer, Andrew ^{[17
]}

Knop, Stefan ^{[18
]}

Bahlis, Nizar J. ^{[19
]}

Renner, Christoph ^{[20
]}

Yu, Xin ^{[21
]}

Hong, Kevin ^{[21
]}

Sternas, Lars ^{[21
]}

Jacques, Christian ^{[21
]}

Zaki, Mohamed H. ^{[21
]}

San Miguel, Jesus F. ^{[22
]}

机构：

[1] Alexandra Hosp, Athens, Greece

[2] Univ Tubingen Hosp, Dept Med, Hematol & Oncol, Tubingen, Germany

[3] Vancouver Gen Hosp, Vancouver, BC, Canada

[4] Univ Hosp Leuven, Dept Hematol, Leuven, Belgium

[5] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Pierre Benite, France

[6] Univ Heidelberg Hosp, Heidelberg, Germany

[7] German Canc Res Ctr, Heidelberg, Germany

[8] Univ Hosp Hotel Dieu, Hematol, Nantes, France

[9] Ctr Hosp Cote Basque, Hematol, Bayonne, France

[10] HGTiP, Inst Catala Oncol, Barcelona, Spain

[11] Hop St Antoine, F-75571 Paris, France

[12] Univ Bologna, Sch Med, Seragnoli Inst Hematol, I-40126 Bologna, Italy

[13] GUZ Moscow City Clin Hosp SP Botkin, Moscow, Russia

[14] Hosp Univ La Princesa, Madrid, Spain

[15] Hosp Univ 12 Octubre, Madrid, Spain

[16] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada

[17] Monash Univ, Alfred Hosp, Melbourne, Vic 3181, Australia

[18] Univ Wurzburg, Wurzburg, Germany

[19] Univ Calgary, Calgary, AB T2N 1N4, Canada

[20] Univ Zurich Hosp, Zurich, Switzerland

[21] Celgene Corp, Summit, NJ USA

[22] Univ Navarra Clin, CIMA, Pamplona, Spain

来源：

HAEMATOLOGICA | 2015年 / 100卷 / 10期

关键词：

STEM-CELL TRANSPLANTATION; HIGH-RISK CYTOGENETICS; INTERGROUPE FRANCOPHONE; PLUS DEXAMETHASONE; BORTEZOMIB; THERAPY; ABNORMALITIES; TRANSLOCATION; DELETION; PROGRESSION;

D O I：

10.3324/haematol.2014.117077

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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).

引用

页码：1327 / 1333

页数：7

共 28 条

[1] Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone [J].

Avet-Loiseau, H. ;

Soulier, J. ;

Fermand, J-P ;

Yakoub-Agha, I. ;

Attal, M. ;

Hulin, C. ;

Garderet, L. ;

Belhadj, K. ;

Dorvaux, V. ;

Minvielle, S. ;

Moreau, P. .

LEUKEMIA, 2010, 24 (03) :623-628

[2] Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome [J].

Avet-Loiseau, Herve ;

Attal, Michel ;

Moreau, Philippe ;

Charbonnel, Catherine ;

Garban, Frederic ;

Hulin, Cyrille ;

Leyvraz, Serge ;

Michallet, Mauricette ;

Yakoub-Agha, Ibrahim ;

Garderet, Laurent ;

Marit, Gerald ;

Michaux, Lucienne ;

Voillat, Laurent ;

Renaud, Marc ;

Grosbois, Bernard ;

Guillerm, Gaelle ;

Benboubker, Lotfi ;

Monconduit, Mathieu ;

Thieblemont, Catherine ;

Casassus, Philippe ;

Caillot, Denis ;

Stoppa, Anne-Marie ;

Sotto, Jean-Jacques ;

Wetterwald, Marc ;

Dumontet, Charles ;

Fuzibet, Jean-Gabriel ;

Azais, Isabelle ;

Dorvaux, Veronique ;

Zandecki, Marc ;

Bataille, Regis ;

Minvielle, Stephane ;

Harousseau, Jean-Luc ;

Facon, Thierry ;

Mathiot, Claire .

BLOOD, 2007, 109 (08) :3489-3495

[3] Chromosomal Abnormalities Are Major Prognostic Factors in Elderly Patients With Multiple Myeloma: The Intergroupe Francophone du Myelome Experience [J].

Avet-Loiseau, Herve ;

Hulin, Cyrille ;

Campion, Loic ;

Rodon, Philippe ;

Marit, Gerald ;

Attal, Michel ;

Royer, Bruno ;

Dib, Mamoun ;

Voillat, Laurent ;

Bouscary, Didier ;

Caillot, Denis ;

Wetterwald, Marc ;

Pegourie, Brigitte ;

Lepeu, Gerard ;

Corront, Bernadette ;

Karlin, Lionel ;

Stoppa, Anne-Marie ;

Fuzibet, Jean-Gabriel ;

Delbrel, Xavier ;

Guilhot, Francois ;

Kolb, Brigitte ;

Decaux, Olivier ;

Lamy, Thierry ;

Garderet, Laurent ;

Allangba, Olivier ;

Lifermann, Francois ;

Anglaret, Bruno ;

Moreau, Philippe ;

Harousseau, Jean-Luc ;

Facon, Thierry .

JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (22) :2806-+

[4] Bortezomib Plus Dexamethasone Induction Improves Outcome of Patients With t(4;14) Myeloma but Not Outcome of Patients With del(17p) [J].

Avet-Loiseau, Herve ;

Leleu, Xavier ;

Roussel, Murielle ;

Moreau, Philippe ;

Guerin-Charbonnel, Catherine ;

Caillot, Denis ;

Marit, Gerald ;

Benboubker, Lotfi ;

Voillat, Laurent ;

Mathiot, Claire ;

Kolb, Brigitte ;

Macro, Margaret ;

Campion, Loic ;

Wetterwald, Marc ;

Stoppa, Anne-Marie ;

Hulin, Cyrille ;

Facon, Thierry ;

Attal, Michel ;

Minvielle, Stephane ;

Harousseau, Jean-Luc .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (30) :4630-4634

[5]

Blade Joan, 1998, British Journal of Haematology, V102, P1115, DOI 10.1046/j.1365-2141.1998.00930.x

[6] Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study [J].

Cavo, Michele ;

Tacchetti, Paola ;

Patriarca, Francesca ;

Petrucci, Maria Teresa ;

Pantani, Lucia ;

Galli, Monica ;

Di Raimondo, Francesco ;

Crippa, Claudia ;

Zamagni, Elena ;

Palumbo, Antonio ;

Offidani, Massimo ;

Corradini, Paolo ;

Narni, Franco ;

Spadano, Antonio ;

Pescosta, Norbert ;

Deliliers, Giorgio Lambertenghi ;

Ledda, Antonio ;

Cellini, Claudia ;

Caravita, Tommaso ;

Tosi, Patrizia ;

Baccarani, Michele .

LANCET, 2010, 376 (9758) :2075-2085

[7] Bortezomib therapy response is independent of cytogenetic abnormalities in relapsed/refractory multiple myeloma [J].

Chang, Hong ;

Trieu, Young ;

Qi, Xiaoying ;

Xu, Wei ;

Stewart, Keith A. ;

Reece, Donna .

LEUKEMIA RESEARCH, 2007, 31 (06) :779-782

[8] The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts [J].

Chesi, M ;

Nardini, E ;

Lim, RSC ;

Smith, KD ;

Kuehl, WM ;

Bergsagel, PL .

BLOOD, 1998, 92 (09) :3025-3034

[9] Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3 [J].

Chesi, M ;

Nardini, E ;

Brents, LA ;

Schrock, E ;

Ried, T ;

Kuehl, WM ;

Bergsagel, PL .

NATURE GENETICS, 1997, 16 (03) :260-264

[10] Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma [J].

Chesi, M ;

Brents, LA ;

Fly, SA ;

Bais, C ;

Robbiani, DF ;

Mesri, E ;

Kuehl, WM ;

Bergsagel, PL .

BLOOD, 2001, 97 (03) :729-736

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