Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone
This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed o...
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| Published in | Leukemia Vol. 24; no. 3; pp. 623 - 628 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.03.2010
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0887-6924 1476-5551 1476-5551 |
| DOI | 10.1038/leu.2009.273 |
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| Abstract | This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence
in situ
hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. |
|---|---|
| AbstractList | This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone.This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. Leukemia (2010) 24, 623-628; doi: 10.1038/leu.2009.273; published online 14 January 2010 Keywords: myeloma; lenalidomide; cytogenetics; FISH; prognosis This retrospective analysis investigated the prognostic value of del(13) and t(4; 14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4; 14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10g per 100ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. |
| Audience | Academic |
| Author | Belhadj, K Yakoub-Agha, I Garderet, L Soulier, J Attal, M Moreau, P Hulin, C Minvielle, S Fermand, J-P Dorvaux, V Avet-Loiseau, H |
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| Keywords | FISH myeloma lenalidomide cytogenetics prognosis Antineoplastic agent High risk Relapse Prognosis Myeloma Immunoglobulinopathy Lymphoproliferative syndrome Fluorescence in situ hybridization Genetics Advanced stage Human Corticosteroid Immunopathology Drug combination Treatment resistance Dexamethasone Hematology Lenalidomide Steroid hormone B cell neoplasm Malignant hemopathy Lymphoid neoplasm Chemotherapy Treatment Cytogenetics Cancer |
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| PublicationTitle | Leukemia |
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| References | Fuchs, Berges, Opelz, Daniel, Naujokat (CR16) 2008; 103 Stadtmauer, Weber, Niesvizky, Belch, Prince, San Miguel (CR13) 2009; 82 Reece, Song, Fu, Roland, Chang, Horsman (CR10) 2009; 114 Kapoor, Kumar, Fonseca, Lacy, Witzig, Hayman (CR11) 2009; 114 Weber, Chen, Niesvizky, Wang, Belch, Stadtmauer (CR4) 2007; 357 Sagaster, Ludwig, Kaufmann, Odelga, Zojer, Ackermann (CR17) 2007; 21 Avet-Loiseau, Attal, Moreau, Charbonnel, Garban, Hulin (CR6) 2007; 109 Wang, Dimopoulos, Chen, Cibeira, Attal, Spencer (CR14) 2008; 112 Jemal, Siegel, Ward, Hao, Xu, Murray (CR1) 2008; 58 Sirohi, Powles (CR2) 2006; 42 Gertz, Lacy, Dispenzieri, Greipp, Litzow, Henderson (CR7) 2005; 106 Debes-Marun, Dewald, Bryant, Picken, Santana-Davila, Gonzalez-Paz (CR8) 2003; 17 Fonseca, Blood, Rue, Harrington, Oken, Kyle (CR5) 2003; 101 Naujokat, Fuchs, Berges (CR15) 2007; 1773 Bladé, Samson, Reece, Apperley, Björkstrand, Gahrton (CR12) 1998; 102 Zonder, Crowley, Bolejack, Hussein, Moore, Whittenberger, Abidi, Durie, Barlogie (CR9) 2008; 26 Dimopoulos, Spencer, Attal, Prince, Harousseau, Dmoszynska (CR3) 2007; 357 Jagannath, Richardson, Sonneveld, Schuster, Irwin, Stadtmauer (CR18) 2007; 21 V Sagaster (BFleu2009273_CR17) 2007; 21 DM Weber (BFleu2009273_CR4) 2007; 357 CS Debes-Marun (BFleu2009273_CR8) 2003; 17 A Jemal (BFleu2009273_CR1) 2008; 58 P Kapoor (BFleu2009273_CR11) 2009; 114 J Bladé (BFleu2009273_CR12) 1998; 102 EA Stadtmauer (BFleu2009273_CR13) 2009; 82 B Sirohi (BFleu2009273_CR2) 2006; 42 H Avet-Loiseau (BFleu2009273_CR6) 2007; 109 D Fuchs (BFleu2009273_CR16) 2008; 103 M Dimopoulos (BFleu2009273_CR3) 2007; 357 R Fonseca (BFleu2009273_CR5) 2003; 101 J. A. Zonder (BFleu2009273_CR9) 2008; 26 M Wang (BFleu2009273_CR14) 2008; 112 MA Gertz (BFleu2009273_CR7) 2005; 106 C Naujokat (BFleu2009273_CR15) 2007; 1773 D Reece (BFleu2009273_CR10) 2009; 114 S Jagannath (BFleu2009273_CR18) 2007; 21 |
| References_xml | – volume: 357 start-page: 2133 year: 2007 end-page: 2142 ident: CR4 article-title: Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America publication-title: N Engl J Med doi: 10.1056/NEJMoa070596 – volume: 21 start-page: 151 year: 2007 end-page: 157 ident: CR18 article-title: Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials publication-title: Leukemia doi: 10.1038/sj.leu.2404442 – volume: 21 start-page: 164 year: 2007 end-page: 168 ident: CR17 article-title: Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion publication-title: Leukemia doi: 10.1038/sj.leu.2404459 – volume: 102 start-page: 1115 year: 1998 end-page: 1123 ident: CR12 article-title: Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. 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Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma publication-title: N Engl J Med doi: 10.1056/NEJMoa070594 – volume: 26 start-page: 8521 issue: 15_suppl year: 2008 end-page: 8521 ident: CR9 article-title: A randomized Southwest Oncology Group study comparing dexamethasone (D) to lenalidomide + dexamethasone (LD) as treatment of newly-diagnosed multiple myeloma (NDMM): Impact of cytogenetic abnormalities on efficacy of LD, and updated overall study results publication-title: Journal of Clinical Oncology doi: 10.1200/jco.2008.26.15_suppl.8521 – volume: 17 start-page: 427 year: 2003 end-page: 436 ident: CR8 article-title: Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma publication-title: Leukemia – volume: 58 start-page: 71 year: 2008 end-page: 96 ident: CR1 article-title: Cancer statistics, 2008 publication-title: CA Cancer J Clin doi: 10.3322/CA.2007.0010 – volume: 112 start-page: 4445 year: 2008 end-page: 4451 ident: CR14 article-title: Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure publication-title: Blood doi: 10.1182/blood-2008-02-141614 – volume: 42 start-page: 1671 year: 2006 end-page: 1683 ident: CR2 article-title: Epidemiology and outcomes research for MGUS, myeloma and amyloidosis publication-title: Eur J Cancer doi: 10.1016/j.ejca.2006.01.065 – volume: 109 start-page: 3489 year: 2007 end-page: 3495 ident: CR6 article-title: Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome publication-title: Blood – volume: 82 start-page: 426 year: 2009 end-page: 432 ident: CR13 article-title: Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma publication-title: Eur J Haematol doi: 10.1111/j.1600-0609.2009.01257.x – volume: 106 start-page: 2837 year: 2005 end-page: 2840 ident: CR7 article-title: Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy publication-title: Blood doi: 10.1182/blood-2005-04-1411 – volume: 114 start-page: 522 year: 2009 ident: BFleu2009273_CR10 publication-title: Blood doi: 10.1182/blood-2008-12-193458 – volume: 21 start-page: 164 year: 2007 ident: BFleu2009273_CR17 publication-title: Leukemia doi: 10.1038/sj.leu.2404459 – volume: 17 start-page: 427 year: 2003 ident: BFleu2009273_CR8 publication-title: Leukemia doi: 10.1038/sj.leu.2402797 – volume: 357 start-page: 2133 year: 2007 ident: BFleu2009273_CR4 publication-title: N Engl J Med doi: 10.1056/NEJMoa070596 – volume: 114 start-page: 518 year: 2009 ident: BFleu2009273_CR11 publication-title: Blood doi: 10.1182/blood-2009-01-202010 – volume: 82 start-page: 426 year: 2009 ident: BFleu2009273_CR13 publication-title: Eur J Haematol doi: 10.1111/j.1600-0609.2009.01257.x – volume: 112 start-page: 4445 year: 2008 ident: BFleu2009273_CR14 publication-title: Blood doi: 10.1182/blood-2008-02-141614 – volume: 21 start-page: 151 year: 2007 ident: BFleu2009273_CR18 publication-title: Leukemia doi: 10.1038/sj.leu.2404442 – volume: 26 start-page: 8521 issue: 15_suppl year: 2008 ident: BFleu2009273_CR9 publication-title: Journal of Clinical Oncology doi: 10.1200/jco.2008.26.15_suppl.8521 – volume: 357 start-page: 2123 year: 2007 ident: BFleu2009273_CR3 publication-title: N Engl J Med doi: 10.1056/NEJMoa070594 – volume: 109 start-page: 3489 year: 2007 ident: BFleu2009273_CR6 publication-title: Blood doi: 10.1182/blood-2006-08-040410 – volume: 106 start-page: 2837 year: 2005 ident: BFleu2009273_CR7 publication-title: Blood doi: 10.1182/blood-2005-04-1411 – volume: 42 start-page: 1671 year: 2006 ident: BFleu2009273_CR2 publication-title: Eur J Cancer doi: 10.1016/j.ejca.2006.01.065 – volume: 103 start-page: 270 year: 2008 ident: BFleu2009273_CR16 publication-title: J Cell Biochem doi: 10.1002/jcb.21405 – volume: 101 start-page: 4569 year: 2003 ident: BFleu2009273_CR5 publication-title: Blood doi: 10.1182/blood-2002-10-3017 – volume: 58 start-page: 71 year: 2008 ident: BFleu2009273_CR1 publication-title: CA Cancer J Clin doi: 10.3322/CA.2007.0010 – volume: 102 start-page: 1115 year: 1998 ident: BFleu2009273_CR12 publication-title: Br J Haematol doi: 10.1046/j.1365-2141.1998.00930.x – volume: 1773 start-page: 1389 year: 2007 ident: BFleu2009273_CR15 publication-title: Biochim Biophys Acta doi: 10.1016/j.bbamcr.2007.05.007 |
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| Title | Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone |
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