Combination of bendamustine, lenalidomide, anddexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: Results of phase 1/2 open-label, doseescalation study

Blood

Volumn 119, Issue 20, 2012, Pages 4608-4613

  Lentzsch, Suzanne ^a   O'Sullivan, Amy ^a   Kennedy, Ryan C ^a   Abbas, Mohammad ^a   Dai, Lijun ^a   Pregja, Silvana Lalo ^b   Burt, Steve ^b   Boyiadzis, Michael ^a   Roodman, G David ^a   Mapara, Markus Y ^a   Agha, Mounzer ^c   Waas, John ^c   Shuai, Yongli ^a   Normolle, Daniel ^a   Zonder, Jeffrey A ^b  

^a UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

^b KARMANOS CANCER INSTITUTE   (United States)

^c UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENDAMUSTINE; BORTEZOMIB; DEXAMETHASONE; LENALIDOMIDE;

ADULT; AGE DISTRIBUTION; AGED; ANEMIA; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER RELAPSE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; FATIGUE; FEMALE; FOLLOW UP; HUMAN; HYPERGLYCEMIA; MALE; MAXIMUM TOLERATED DOSE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NEUTROPENIA; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGNOSIS; PROGRESSION FREE SURVIVAL; RECURRENT DISEASE; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE;

EID: 84861208513     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2011-12-395715     Document Type: Article

References (24)

1. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood. 2008;111(5): 2521-2526.
2. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111(5):2516- 2520.
3. Altekruse SF, Kosary CL, Krapcho M, et al, eds. SEER Cancer Statistics Review, 1975-2007. Bethesda, MD: National Cancer Institute; 2010.
4. Zhu YX, Braggio E, Shi CX, et al. Cereblon expression is required for the anti-myeloma activity of lenalidomide and pomalidomide. Blood. 2011; 118(18):4771-4779.
5. Li S, Pal R, Monaghan SA, et al. IMiD immunomodulatory compounds block C/EBPβ translation through eIF4E down-regulation resulting in inhibition of MM. Blood. 2011;117(19):5157-5165.
6. Lopez-Girona A, Heintel D, Zhang LH, et al. Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br J Haematol. 2011;154(3):325-336.
7. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007; 357(21):2123-2132. (Pubitemid 350146107)
8. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007; 357(21):2133-2142. (Pubitemid 350146108)
9. Dimopoulos MA, Chen C, Spencer A, et al. Longterm follow-up on overall survival from the MM- 009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009; 23(11):2147-2152.
10. Gaul L, Mandl-Weber S, Baumann P, Emmerich B, Schmidmaier R. Bendamustine induces G2 cell cycle arrest and apoptosis in myeloma cells: the role ofATM-Chk2-Cdc25A andATM-p53-p21-pathways. J Cancer Res Clin Oncol. 2008;134(2):245-253. (Pubitemid 350234070)
11. Ponisch W, Mitrou PS, Merkle K, et al. Treatment of Bendamustine and Prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with Melphalan and Prednisone: a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol. 2006; 132(4):205-212. (Pubitemid 43144255)
12. Knop S, Straka C, Haen M, Schwedes R, Hebart H, Einsele H. The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high-dose chemotherapy. Haematologica. 2005;90(9):1287-1288. (Pubitemid 41375295)
13. Ponisch W, Rozanski M, Goldschmidt H, et al. Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a Phase I clinical trial. Br J Haematol. 2008;143(2):191-200.
14. Fayers PM, Palumbo A, Hulin C, et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011;118(5):1239-1247.
15. Kapoor P, Rajkumar SV, Dispenzieri A, et al. Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a metaanalysis. Leukemia. 2011;25(4):689-696.
16. Palumbo A, Falco P, Corradini P, et al. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA-Italian Multiple Myeloma Network. J Clin Oncol. 2007;25(28):4459-4465. (Pubitemid 350063804)
17. Dispenzieri A, Kyle R, Merlini G, et al. International MyelomaWorking Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23(2):215-224.
18. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467-1473. (Pubitemid 44264086)
19. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23(1):3-9.
20. Rajkumar SV, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691-4695.
21. Blade J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by highdose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT: European Group for Blood and Marrow Transplant. Br J Haematol. 1998;102(5):1115-1123. (Pubitemid 28435189)
22. Fenk R, Michael M, Zohren F, et al. Escalation therapy with bortezomib, dexamethasone and bendamustine for patients with relapsed or refractory multiple myeloma. Leuk Lymphoma. 2007;48(12):2345-2351. (Pubitemid 350253466)
23. Weide R. Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin's lymphoma. Ther Clin Risk Manag. 2008;4(4):727-732.
24. Ramasamy K, Hazel B, Mahmood S, Corderoy S, Schey S. Bendamustine in combination with thalidomide and dexamethasone is an effective therapy for myeloma patients with end stage renal disease. Br J Haematol. 2011;155(5):632-634.