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12 - Treatment of relapsed/refractory myeloma

from Section 3 - Myeloma: clinical entities

Published online by Cambridge University Press:  18 December 2013

By
Matthew J. Streetly ,
Jacob Laubach ,
Paul Richardson  and
Stephen A. Schey
Edited by
Stephen A. Schey ,
Kwee L. Yong ,
Robert Marcus  and
Kenneth C. Anderson
Stephen A. Schey
Affiliation:
Department of Haematology, King’s College Hospital, London
Kwee L. Yong
Affiliation:
Department of Haematology, University College Hospital, London
Robert Marcus
Affiliation:
Department of Haematology, King’s College Hospital, London
Kenneth C. Anderson
Affiliation:
Dana-Farber Cancer Institute, Boston
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Summary

Introduction

Modern treatment of newly diagnosed MM has led to improved responses and markedly improved survival[1,2]. However, despite excellent responses and disease control most patients will eventually relapse and require further therapy. Management of relapsed disease is therefore a critical aspect of overall care. This chapter provides a comprehensive overview of the determinants of and general approaches to therapy as well as a review of specific treatment regimens.

Definition of relapsed and relapsed/refractory MM

The European Group for Blood and Marrow Transplantation (EBMT)[3] criteria and International Myeloma Working Group (IMWG) uniform criteria[4] define progressive disease as ≥25% increase (or reappearance from complete response) in the measurable biochemical component (serum monoclonal protein, urine Bence Jones protein or Serum Free Light chain), an increase in bone marrow plasma cells to >10% or the development of new lytic bone lesions/soft tissue plasmacytomas. Clinical relapse is defined as the development of progressive disease and/or myeloma associated end organ dysfunction (CRAB criteria). Primary refractory myeloma refers to disease that fails to achieve at least a minimal response (MR) with initial therapy whilst relapsed and refractory MM is defined as disease that is non-responsive to salvage therapy, or progresses within 60 days of last treatment in patients who previously achieved at least a minimal response (MR).

Type
Chapter
Information
Myeloma
Pathology, Diagnosis, and Treatment
 , pp. 144 - 166
Publisher: Cambridge University Press
Print publication year: 2013

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References

Kumar, S. K., Rajkumar, S. V., Dispenzieri, A. et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516–20.CrossRefGoogle ScholarPubMed
Venner, C. P., Connors, J. M., Sutherland, H. J. et al. Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (<12 months). Leuk. Lymphoma 2011;52:34–41.CrossRefGoogle Scholar
Blade, J., Samson, D., Reece, D. et al. 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. Br. J. Haematol. 1998;102:1115–23.CrossRefGoogle ScholarPubMed
Durie, B. G., Harousseau, J. L., Miguel, J. S. et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467–73.CrossRefGoogle ScholarPubMed
Rajkumar, S. V., Harousseau, J. L., Durie, B. et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood; 117:4691–5.CrossRef
Avet-Loiseau, H., Soulier, J., Fermand, J. P. et al. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia 2010;24:623–8.CrossRefGoogle ScholarPubMed
Conner, T. M., Doan, Q. D., Walters, I. B., LeBlanc, A. L., Beveridge, R. A.An observational, retrospective analysis of retreatment with bortezomib for multiple myeloma. Clin. Lymphoma Myeloma 2008;8:140–5.CrossRefGoogle ScholarPubMed
Barlogie, B., Smith, L., Alexanian, R.Effective treatment of advanced multiple myeloma refractory to alkylating agents. N. Engl. J. Med. 1984;310:1353–6.CrossRefGoogle ScholarPubMed
Bonnet, J., Alexanian, R., Salmon, S. et al. Vincristine, BCNU, doxorubicin, and prednisone (VBAP) combination in the treatment of relapsing or resistant multiple myeloma: a Southwest Oncology Group study. Cancer Treat. Rep. 1982;66:1267–71.Google ScholarPubMed
Dimopoulos, M. A., Weber, D., Kantarjian, H., Delasalle, K. B., Alexanian, R.HyperCVAD for VAD-resistant multiple myeloma. Am. J. Hematol. 1996;52:77–81.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Forgeson, G. V., Selby, P., Lakhani, S. et al. Infused vincristine and adriamycin with high dose methylprednisolone (VAMP) in advanced previously treated multiple myeloma patients. Br. J. Cancer 1988;58:469–73.CrossRefGoogle ScholarPubMed
Giles, F. J., Wickham, N. R., Rapoport, B. L. et al. Cyclophosphamide, etoposide, vincristine, adriamycin, and dexamethasone (CEVAD) regimen in refractory multiple myeloma: an International Oncology Study Group (IOSG) phase II protocol. Am. J. Hematol. 2000;63:125–30.3.0.CO;2-S>CrossRefGoogle Scholar
Lokhorst, H. M., Meuwissen, O. J., Bast, E. J., Dekker, A. W.VAD chemotherapy for refractory multiple myeloma. Br. J. Haematol. 1989;71:25–30.CrossRefGoogle ScholarPubMed
Phillips, J. K., Sherlaw-Johnson, C., Pearce, R. et al. A randomized study of MOD versus VAD in the treatment of relapsed and resistant multiple myeloma. Leuk. Lymphoma 1995;17:465–72.CrossRefGoogle ScholarPubMed
Sonneveld, P., Schoester, M., de Leeuw, K.Clinical modulation of multidrug resistance in multiple myeloma: effect of cyclosporine on resistant tumor cells. J. Clin. Oncol. 1994;12:1584–91.CrossRefGoogle ScholarPubMed
Dalton, W. S., Crowley, J. J., Salmon, S. S. et al. A phase III randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in patients with refractory myeloma. A Southwest Oncology Group study. Cancer 1995;75:815–20.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Gertz, M. A., Kalish, L. A., Kyle, R. A. et al. Phase III study comparing vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) chemotherapy with VAD plus recombinant interferon alfa-2 in refractory or relapsed multiple myeloma. An Eastern Cooperative Oncology Group study. Am. J. Clin. Oncol. 1995;18:475–80.Google ScholarPubMed
Friedenberg, W. R., Rue, M., Blood, E. A. et al. Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): a trial of the Eastern Cooperative Oncology Group. Cancer 2006;106:830–8.CrossRefGoogle ScholarPubMed
Cavo, M., Galieni, P., Tassi, C., Gobbi, M., Tura, S.M-2 protocol for melphalan-resistant and relapsing multiple myeloma. Eur. J. Haematol. 1988;40:168–73.CrossRefGoogle ScholarPubMed
Sumpter, K., Powles, R. L., Raje, N. et al. Oral idarubicin as a single agent therapy in patients with relapsed or resistant multiple myeloma. Leuk. Lymphoma 1999;35:593–7.CrossRefGoogle ScholarPubMed
Parameswaran, R., Giles, C., Boots, M. et al. CCNU (lomustine), idarubicin and dexamethasone (CIDEX): an effective oral regimen for the treatment of refractory or relapsed myeloma. Br. J. Haematol. 2000;109:571–5.CrossRefGoogle ScholarPubMed
Alexanian, R., Barlogie, B., Dixon, D.High-dose glucocorticoid treatment of resistant myeloma. Ann. Intern. Med. 1986;105:8–11.CrossRefGoogle ScholarPubMed
Dimopoulos, M., Spencer, A., Attal, M. et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N. Engl. J. Med. 2007;357:2123–32.CrossRefGoogle ScholarPubMed
Richardson, P. G., Sonneveld, P., Schuster, M. W. et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N. Engl. J. Med. 2005;352:2487–98.CrossRefGoogle ScholarPubMed
Weber, D. M., Chen, C., Niesvizky, R. et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N. Engl. J. Med. 2007;357:2133–42.CrossRefGoogle ScholarPubMed
Tiplady, C. W., Summerfield, G. P.Continuous low-dose dexamethasone in relapsed or refractory multiple myeloma. Br. J. Haematol. 2000;111:381.CrossRefGoogle ScholarPubMed
Gertz, M. A., Garton, J. P., Greipp, P. R., Witzig, T. E., Kyle, R. A.A phase II study of high-dose methylprednisolone in refractory or relapsed multiple myeloma. Leukemia 1995;9:2115–18.Google ScholarPubMed
Back, H., Lindblad, R., Rodjer, S., Westin, J.Single-dose intravenous melphalan in advanced multiple myeloma. Acta Haematol. 1990;83:183–6.CrossRefGoogle ScholarPubMed
Maniatis, A., Tsakanikas, S., Stamatellou, M., Papanastasiou, K.Intermediate-dose melphalan for refractory myeloma. Blood 1989;74:1177.Google ScholarPubMed
Petrucci, M. T., Avvisati, G., Tribalto, M. et al. Intermediate-dose (25 mg/m2) intravenous melphalan for patients with multiple myeloma in relapse or refractory to standard treatment. Eur. J. Haematol. 1989;42:233–7.CrossRefGoogle ScholarPubMed
Tsakanikas, S., Papanastasiou, K., Stamatelou, M., Maniatis, A.Intermediate dose of intravenous melphalan in advanced multiple myeloma. Oncology 1991;48:369–71.CrossRefGoogle ScholarPubMed
Dumontet, C., Jaubert, J., Sebban, C. et al. Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients. Ann. Oncol. 2003;14:615–22.CrossRefGoogle ScholarPubMed
Mangiacavalli, S., Pica, G., Varettoni, M., Lazzarino, M., Corso, A.Efficacy and safety of fotemustine for the treatment of relapsed and refractory multiple myeloma patients. Eur. J. Haematol. 2009;82:240–1.CrossRefGoogle ScholarPubMed
Barlogie, B., Velasquez, W. S., Alexanian, R., Cabanillas, F.Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma. J. Clin. Oncol. 1989;7:1514–17.CrossRefGoogle ScholarPubMed
Dadacaridou, M., Papanicolaou, X., Maltesas, D. et al. Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) for relapsed or refractory multiple myeloma patients. J. BUON 2007;12:41–4.Google ScholarPubMed
D’Sa, S., Yong, K., Kyriakou, C. et al. Etoposide, methylprednisolone, cytarabine and cisplatin successfully cytoreduces resistant myeloma patients and mobilizes them for transplant without adverse effects. Br. J. Haematol. 2004;125:756–65.CrossRefGoogle ScholarPubMed
Singhal, S., Mehta, J., Desikan, R. et al. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 1999;341:1565–71.CrossRefGoogle ScholarPubMed
Barlogie, B., Desikan, R., Eddlemon, P. et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001;98:492–4.CrossRefGoogle Scholar
Cibeira, M. T., Rosinol, L., Ramiro, L. et al. Long-term results of thalidomide in refractory and relapsed multiple myeloma with emphasis on response duration. Eur. J. Haematol. 2006;77:486–92.CrossRefGoogle ScholarPubMed
Fenk, R., Hoyer, B., Steidl, U. et al. Single-agent thalidomide for treatment of first relapse following high-dose chemotherapy in patients with multiple myeloma. Leukemia 2005;19:156–9.CrossRefGoogle ScholarPubMed
Hattori, Y., Okamoto, S., Shimada, N. et al. Single-institute phase 2 study of thalidomide treatment for refractory or relapsed multiple myeloma: prognostic factors and unique toxicity profile. Cancer Sci. 2008;99:1243–50.CrossRefGoogle ScholarPubMed
Huang, S. Y., Tang, J. L., Yao, M. et al. Reduction of leukocyte count is associated with thalidomide response in treatment of multiple myeloma. Ann Hematol. 2003;82:558–64.CrossRefGoogle ScholarPubMed
Hus, I., Dmoszynska, A., Manko, J. et al. An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma. Br. J. Cancer 2004;91:1873–9.CrossRefGoogle ScholarPubMed
Hus, M., Dmoszynska, A., Soroka-Wojtaszko, M. et al. Thalidomide treatment of resistant or relapsed multiple myeloma patients. Haematologica 2001;86:404–8.Google ScholarPubMed
Juliusson, G., Celsing, F., Turesson, I. et al. Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma. Br. J. Haematol. 2000;109:89–96.CrossRefGoogle ScholarPubMed
Kees, M., Dimou, G., Sillaber, C. et al. Low dose thalidomide in patients with relapsed or refractory multiple myeloma. Leuk. Lymphoma 2003;44:1943–6.CrossRefGoogle ScholarPubMed
Kumar, S., Gertz, M. A., Dispenzieri, A. et al. Response rate, durability of response, and survival after thalidomide therapy for relapsed multiple myeloma. Mayo Clin. Proc. 2003;78:34–9.CrossRefGoogle ScholarPubMed
Maisnar, V., Radocha, J., Buchler, T. et al. Monotherapy with low-dose thalidomide for relapsed or refractory multiple myeloma: better response rate with earlier treatment. Eur. J. Haematol. 2007;79:305–9.CrossRefGoogle ScholarPubMed
Mileshkin, L., Biagi, J. J., Mitchell, P. et al. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood 2003;102:69–77.CrossRefGoogle ScholarPubMed
Mohty, M., Attal, M., Marit, G. et al. Thalidomide salvage therapy following allogeneic stem cell transplantation for multiple myeloma: a retrospective study from the Intergroupe Francophone du Myelome (IFM) and the Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC). Bone Marrow Transplant. 2005;35:165–9.CrossRefGoogle Scholar
Neben, K., Moehler, T., Benner, A. et al. Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma. Clin. Cancer Res. 2002;8:3377–82.Google ScholarPubMed
Richardson, P., Schlossman, R., Jagannath, S. et al. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity. Mayo Clin. Proc. 2004;79:875–82.CrossRefGoogle ScholarPubMed
Rosinol, L., Cibeira, M. T., Blade, J. et al. Extramedullary multiple myeloma escapes the effect of thalidomide. Haematologica 2004;89:832–6.Google ScholarPubMed
Schey, S. A., Cavenagh, J., Johnson, R. et al. A UK myeloma forum phase II study of thalidomide; long term follow-up and recommendations for treatment. Leuk. Res. 2003;27:909–14.CrossRefGoogle Scholar
Tosi, P., Zamagni, E., Cellini, C. et al. Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma. Haematologica 2002;87:408–14.Google ScholarPubMed
Waage, A., Gimsing, P., Juliusson, G. et al. Early response predicts thalidomide efficiency in patients with advanced multiple myeloma. Br. J. Haematol. 2004;125:149–55.CrossRefGoogle ScholarPubMed
Wechalekar, A. D., Chen, C. I., Sutton, D. et al. Intermediate dose thalidomide (200 mg daily) has comparable efficacy and less toxicity than higher doses in relapsed multiple myeloma. Leuk. Lymphoma 2003;44:1147–9.CrossRefGoogle ScholarPubMed
Yakoub-Agha, I., Attal, M., Dumontet, C. et al. Thalidomide in patients with advanced multiple myeloma: a study of 83 patients–report of the Intergroupe Francophone du Myelome (IFM). Hematol. J. 2002;3:185–92.CrossRefGoogle Scholar
Glasmacher, A., Hahn, C., Hoffmann, F. et al. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br. J. Haematol. 2006;132:584–93.CrossRefGoogle ScholarPubMed
Prince, H. M., Schenkel, B., Mileshkin, L.An analysis of clinical trials assessing the efficacy and safety of single-agent thalidomide in patients with relapsed or refractory multiple myeloma. Leuk. Lymphoma 2007;48:46–55.CrossRefGoogle ScholarPubMed
Kropff, M., Baylon, H. G., Hillengass, J. et al. Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica 2012;97:784–91.CrossRefGoogle ScholarPubMed
Dimopoulos, M. A., Zervas, K., Kouvatseas, G. et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol. 2001;12:991–5.CrossRefGoogle ScholarPubMed
von Lilienfeld-Toal, M., Hahn-Ast, C., Furkert, K. et al. A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. Eur. J. Haematol. 2008;81:247–52.CrossRefGoogle ScholarPubMed
Dimopoulos, M. A., Hamilos, G., Zomas, A. et al. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. Hematol. J. 2004;5:112–17.CrossRefGoogle ScholarPubMed
Garcia-Sanz, R., Gonzalez-Porras, J. R., Hernandez, J. M. et al. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. Leukemia 2004;18:856–63.CrossRefGoogle ScholarPubMed
Kropff, M. H., Lang, N., Bisping, G. et al. Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Br. J. Haematol. 2003;122:607–16.CrossRefGoogle ScholarPubMed
Kyriakou, C., Thomson, K., D’Sa, S. et al. Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. Br. J. Haematol. 2005;129:763–70.CrossRefGoogle ScholarPubMed
Roussou, M., Anagnostopoulos, A., Kastritis, E. et al. Pulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously treated patients with multiple myeloma: long term follow up and disease control after subsequent treatments. Leuk. Lymphoma 2007;48:754–8.CrossRefGoogle ScholarPubMed
Sidra, G., Williams, C. D., Russell, N. H. et al. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma. Haematologica 2006;91:862–3.Google ScholarPubMed
Suvannasankha, A., Fausel, C., Juliar, B. E. et al. Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: A Hoosier Oncology Group Trial, HEM01–21. Oncologist 2007;12:99–106.CrossRefGoogle ScholarPubMed
Offidani, M., Corvatta, L., Marconi, M. et al. Thalidomide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma. Hematol. J. 2004;5:312–17.CrossRefGoogle ScholarPubMed
Palumbo, A., Avonto, I., Bruno, B. et al. Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma. Eur. J. Haematol. 2006;76:273–7.CrossRefGoogle ScholarPubMed
Srkalovic, G., Elson, P., Trebisky, B., Karam, M. A., Hussein, M. A.Use of melphalan, thalidomide, and dexamethasone in treatment of refractory and relapsed multiple myeloma. Med. Oncol. 2002;19:219–26.CrossRefGoogle ScholarPubMed
Offidani, M., Bringhen, S., Corvatta, L. et al. Thalidomide-dexamethasone plus pegylated liposomal doxorubicin vs. thalidomide-dexamethasone: a case-matched study in advanced multiple myeloma. Eur. J. Haematol. 2007;78:297–302.CrossRefGoogle ScholarPubMed
Chang, D. H., Liu, N., Klimek, V. et al. Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood 2006;108:618–21.CrossRefGoogle ScholarPubMed
Davies, F. E., Raje, N., Hideshima, T. et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98:210–16.CrossRefGoogle ScholarPubMed
Dredge, K., Horsfall, R., Robinson, S. P. et al. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc. Res. 2005;69:56–63.CrossRefGoogle ScholarPubMed
LeBlanc, R., Hideshima, T., Catley, L. P. et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood 2004;103:1787–90.CrossRefGoogle ScholarPubMed
Mitsiades, N., Mitsiades, C. S., Poulaki, V. et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99:4525–30.CrossRefGoogle ScholarPubMed
Richardson, P. G., Schlossman, R. L., Weller, E. et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002;100:3063–7.CrossRefGoogle ScholarPubMed
Richardson, P. G., Blood, E., Mitsiades, C. S. et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006;108:3458–64.CrossRefGoogle ScholarPubMed
Richardson, P., Jagannath, S., Hussein, M. et al. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 2009;114:772–8.CrossRefGoogle ScholarPubMed
Reece, D., Song, K. W., Fu, T. et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood 2009;114:522–5.CrossRefGoogle ScholarPubMed
Schey, S. A., Morgan, G. J., Ramasamy, K. et al. The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study. Br. J. Haematol. 2010;150:326–33.CrossRefGoogle ScholarPubMed
Myung, J., Kim, K. B., Crews, C. M.The ubiquitin-proteasome pathway and proteasome inhibitors. Med. Res. Rev. 2001;21:245–73.CrossRefGoogle ScholarPubMed
Mitsiades, N., Mitsiades, C. S., Poulaki, V. et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc. Natl Acad. Sci. USA 2002;99:14 374–9.CrossRefGoogle ScholarPubMed
Moreau, P., Pylypenko, H., Grosicki, S. et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol.;12:431–40.CrossRef
Orlowski, R. Z., Stinchcombe, T. E., Mitchell, B. S. et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J. Clin. Oncol. 2002;20:4420–7.CrossRefGoogle ScholarPubMed
Richardson, P. G., Sonneveld, P., Schuster, M. et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 2007;110:3557–60.CrossRefGoogle ScholarPubMed
Ma, M. H., Yang, H. H., Parker, K. et al. The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. Clin. Cancer Res. 2003;9:1136–44.Google ScholarPubMed
Mitsiades, N., Mitsiades, C. S., Richardson, P. G. et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 2003;101:2377–80.CrossRefGoogle ScholarPubMed
Jagannath, S., Barlogie, B., Berenson, J. et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br. J. Haematol. 2004;127:165–72.CrossRefGoogle ScholarPubMed
Richardson, P. G., Barlogie, B., Berenson, J. et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med. 2003;348:2609–17.CrossRefGoogle ScholarPubMed
Jagannath, S., Richardson, P. G., Sonneveld, P. et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia 2007;21:151–7.CrossRefGoogle ScholarPubMed
Chang, H., Trieu, Y., Qi, X. et al. Bortezomib therapy response is independent of cytogenetic abnormalities in relapsed/refractory multiple myeloma. Leuk. Res. 2007;31:779–82.CrossRefGoogle ScholarPubMed
Sagaster, V., Ludwig, H., Kaufmann, H. et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia 2007;21:164–8.CrossRefGoogle ScholarPubMed
Richardson, P. G., Barlogie, B., Berenson, J. et al. Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma. Blood 2005;106:2977–81.CrossRefGoogle ScholarPubMed
Orlowski, R. Z., Nagler, A., Sonneveld, P. et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J. Clin. Oncol. 2007;25:3892–901.CrossRefGoogle ScholarPubMed
Blade, J., Sonneveld, P., San Miguel, J. F. et al. Pegylated liposomal doxorubicin plus bortezomib in relapsed or refractory multiple myeloma: efficacy and safety in patients with renal function impairment. Clin. Lymphoma Myeloma 2008;8:352–5.CrossRefGoogle ScholarPubMed
Palumbo, A., Gay, F., Bringhen, S. et al. Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma. Ann. Oncol. 2008;19:1160–5.CrossRefGoogle ScholarPubMed
Reece, D. E., Rodriguez, G. P., Chen, C. et al. Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. J. Clin. Oncol. 2008;26:4777–83.CrossRefGoogle ScholarPubMed
Davies, F. E., Wu, P., Jenner, M. et al. The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Haematologica 2007;92:1149–50.CrossRefGoogle ScholarPubMed
Fu, W., Delasalle, K., Wang, J. et al. Bortezomib-cyclophosphamide-dexamethasone for relapsing multiple myeloma. Am. J. Clin. Oncol. 2012;35:562–5.CrossRefGoogle ScholarPubMed
Kropff, M., Bisping, G., Schuck, E. et al. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br. J. Haematol. 2007;138:330–7.CrossRefGoogle ScholarPubMed
Popat, R., Oakervee, H., Williams, C. et al. Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma. Br. J. Haematol. 2009;144:887–94.CrossRefGoogle ScholarPubMed
Chanan-Khan, A., Miller, K. C.Velcade, Doxil and Thalidomide (VDT) is an effective salvage regimen for patients with relapsed and refractory multiple myeloma. Leuk. Lymphoma 2005;46:1103–4.CrossRefGoogle ScholarPubMed
Chanan-Khan, A., Miller, K. C., Musial, L. et al. Bortezomib in combination with pegylated liposomal doxorubicin and thalidomide is an effective steroid independent salvage regimen for patients with relapsed or refractory multiple myeloma: results of a phase II clinical trial. Leuk Lymphoma 2009;50:1096–101.CrossRefGoogle ScholarPubMed
Ciolli, S., Leoni, F., Gigli, F., Rigacci, L., Bosi, A.Low dose velcade, thalidomide and dexamethasone (LD-VTD): an effective regimen for relapsed and refractory multiple myeloma patients. Leuk. Lymphoma 2006;47:171–3.CrossRefGoogle ScholarPubMed
Kim, Y. K., Sohn, S. K., Lee, J. H. et al. Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study. Ann. Hematol. 2010;89:475–82.CrossRefGoogle ScholarPubMed
Offidani, M., Corvatta, L., Polloni, C. et al. Thalidomide, dexamethasone, doxil and velcade (ThaDD-V) followed by consolidation/maintenance therapy in patients with relapsed-refractory multiple myeloma. Ann. Hematol. 2011;90:1449–56.CrossRefGoogle ScholarPubMed
Palumbo, A., Ambrosini, M. T., Benevolo, G. et al. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood 2007;109:2767–72.Google ScholarPubMed
Pineda-Roman, M., Zangari, M., van Rhee, F. et al. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma. Leukemia 2008;22:1419–27.CrossRefGoogle ScholarPubMed
Lee, C. K., Barlogie, B., Munshi, N. et al. DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J. Clin. Oncol. 2003;21:2732–9.CrossRefGoogle ScholarPubMed
Garderet, L., Iacobelli, S., Moreau, P. et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005–04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J. Clin. Oncol. 2012; 30:2475–82.CrossRefGoogle ScholarPubMed
Richardson, P. G., Weller, E., Jagannath, S. et al. Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma. J. Clin. Oncol. 2009;27:5713–19.CrossRefGoogle ScholarPubMed
Baz, R., Walker, E., Karam, M. A. et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann. Oncol. 2006;17:1766–71.CrossRefGoogle ScholarPubMed
Palumbo, A., Larocca, A., Falco, P. et al. Lenalidomide, melphalan, prednisone and thalidomide (RMPT) for relapsed/refractory multiple myeloma. Leukemia 2010;24:1037–42.CrossRefGoogle ScholarPubMed
Alexanian, R., Dimopoulos, M. A., Hester, J., Delasalle, K., Champlin, R.Early myeloablative therapy for multiple myeloma. Blood 1994;84:4278–82.Google ScholarPubMed
Alexanian, R., Weber, D., Delasalle, K. et al. Clinical outcomes with intensive therapy for patients with primary resistant multiple myeloma. Bone Marrow Transplant 2004;34:229–34.CrossRefGoogle ScholarPubMed
Kumar, S., Lacy, M. Q., Dispenzieri, A. et al. High-dose therapy and autologous stem cell transplantation for multiple myeloma poorly responsive to initial therapy. Bone Marrow Transplant 2004;34:161–7.CrossRefGoogle ScholarPubMed
Rajkumar, S. V., Fonseca, R., Lacy, M. Q. et al. Autologous stem cell transplantation for relapsed and primary refractory myeloma. Bone Marrow Transplant 1999;23:1267–72.CrossRefGoogle ScholarPubMed
Rosinol, L., Garcia-Sanz, R., Lahuerta, J. J. et al. Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease. Haematologica 2012;97:616–21.CrossRefGoogle ScholarPubMed
Singhal, S., Powles, R., Sirohi, B. et al. Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma. Bone Marrow Transplant 2002;30:673–9.CrossRefGoogle ScholarPubMed
Lee, C. K., Barlogie, B., Zangari, M. et al. Transplantation as salvage therapy for high-risk patients with myeloma in relapse. Bone Marrow Transplant 2002;30:873–8.CrossRefGoogle ScholarPubMed
Mansi, J. L., Cunningham, D., Viner, C. et al. Repeat administration of high dose melphalan in relapsed myeloma. Br. J. Cancer 1993;68:983–7.CrossRefGoogle ScholarPubMed
Alvares, C. L., Davies, F. E., Horton, C. et al. The role of second autografts in the management of myeloma at first relapse. Haematologica 2006;91:141–2.Google ScholarPubMed
Olin, R. L., Vogl, D. T., Porter, D. L. et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transplant 2009;43:417–22.CrossRefGoogle ScholarPubMed
Cook, G., Liakopoulou, E., Pearce, R. et al. Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol. Blood Marrow Transplant 2011;17:1638–45.CrossRefGoogle ScholarPubMed
Tricot, G., Vesole, D. H., Jagannath, S. et al. Graft-versus-myeloma effect: proof of principle. Blood 1996;87:1196–8.Google ScholarPubMed
Gahrton, G., Svensson, H., Cavo, M. et al. Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983–93 and 1994–8 at European Group for Blood and Marrow Transplantation centres. Br. J. Haematol. 2001;113:209–16.CrossRefGoogle Scholar
Lokhorst, H., Einsele, H., Vesole, D. et al. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J. Clin. Oncol. 2010;28:4521–30.CrossRefGoogle Scholar
Bremer, K.High rates of long-lasting remissions after 5-day bendamustine chemotherapy cycles in pre-treated low-grade non-Hodgkin’s-lymphomas. J. Cancer Res. Clin. Oncol. 2002;128:603–9.CrossRefGoogle ScholarPubMed
Damaj, G., Malard, F., Hulin, C. et al. Efficacy of bendamustine in relapsed/refractory myeloma patients: results from the French compassionate use program. Leuk. Lymphoma 2012;53:632–4.CrossRefGoogle ScholarPubMed
Knop, S., Straka, C., Haen, M. et al. The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high-dose chemotherapy. Haematologica 2005;90:1287–8.Google ScholarPubMed
Michael, M., Bruns, I., Bolke, E. et al. Bendamustine in patients with relapsed or refractory multiple myeloma. Eur. J. Med. Res. 2010;15:13–19.CrossRefGoogle ScholarPubMed
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;143:191–200.CrossRefGoogle ScholarPubMed
Bartlett, J. B., Dredge, K., Dalgleish, A. G.The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat. Rev. Cancer 2004;4:314–22.CrossRefGoogle Scholar
Hideshima, T., Chauhan, D., Shima, Y. et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000;96:2943–50.Google ScholarPubMed
Gupta, D., Treon, S. P., Shima, Y. et al. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia 2001;15:1950–61.CrossRefGoogle ScholarPubMed
Corral, L. G., Haslett, P. A., Muller, G. W. et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J. Immunol. 1999;163:380–6.Google Scholar
Haslett, P. A., Corral, L. G., Albert, M., Kaplan, G.Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J. Exp. Med. 1998;187:1885–92.CrossRefGoogle Scholar
Muller, G. W., Chen, R., Huang, S. Y. et al. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg. Med. Chem. Lett. 1999;9:1625–30.CrossRefGoogle ScholarPubMed
Schey, S. A., Fields, P., Bartlett, J. B. et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J. Clin. Oncol. 2004;22:3269–76.CrossRefGoogle ScholarPubMed
Streetly, M. J., Gyertson, K., Daniel, Y. et al. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br. J. Haematol. 2008;141:41–51.CrossRefGoogle ScholarPubMed
Lacy, M. Q., Hayman, S. R., Gertz, M. A. et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J. Clin. Oncol. 2009;27:5008–14.CrossRefGoogle ScholarPubMed
Lacy, M. Q., Hayman, S. R., Gertz, M. A. et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia 2010;24:1934–9.CrossRefGoogle Scholar
Lacy, M. Q., Allred, J. B., Gertz, M. A. et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood 2011;118:2970–5.CrossRefGoogle ScholarPubMed
Richardson, P. G., Siegel, D. S., Vij, R. et al. Randomized, open label phase 1/2 study of pomalidomide (POM) alone or in combination with low-dose dexamethasone (LoDex) in patients (Pts) with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide (LEN) and bortezomib (BORT): phase 2 results. ASH Annual Meeting Abstracts 2011;118:634.Google Scholar
Gallinari, P., Di Marco, S., Jones, P., Pallaoro, M., Steinkuhler, C.HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics. Cell Res. 2007;17:195–211.CrossRefGoogle ScholarPubMed
Roth, S. Y., Denu, J. M., Allis, C. D.Histone acetyltransferases. Ann. Rev. Biochem. 2001;70:81–120.CrossRefGoogle ScholarPubMed
Minucci, S., Pelicci, P. G.Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer 2006;6:38–51.CrossRefGoogle ScholarPubMed
Niesvizky, R., Ely, S., Mark, T. et al. Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma. Cancer 2011;117:336–42.CrossRefGoogle ScholarPubMed
Richardson, P., Mitsiades, C., Colson, K. et al. Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma. Leuk. Lymphoma 2008;49:502–7.CrossRefGoogle ScholarPubMed
Wolf, J. L., Siegel, D., Matous, J. et al. A phase II study of oral panobinostat (LBH589) in adult patients with advanced refractory multiple myeloma. ASH Annual Meeting Abstracts 2008;112:2774.Google Scholar
Siegel, D. S., Dimopoulos, M. A., Yoon, S.-S. et al. Vantage 095: vorinostat in combination with bortezomib in salvage multiple myeloma patients: final study results of a global phase 2b trial. ASH Annual Meeting Abstracts 2011;118:480.Google Scholar
Dimopoulos, M. A., Jagannath, S., Yoon, S.-S. et al. Vantage 088: vorinostat in combination with bortezomib in patients with relapsed/refractory multiple myeloma: results of a global, randomized phase 3 trial. ASH Annual Meeting Abstracts 2011;118:811.Google Scholar
Richardson, P., Weber, D., Mitsiades, C. S. et al. A phase I study of vorinostat, lenalidomide, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: excellent tolerability and promising activity in a heavily pretreated population. ASH Annual Meeting Abstracts 2010;116:1951.Google Scholar
Richardson, P. G., Alsina, M., Weber, D. M. et al. Phase II study of the pan-deacetylase inhibitor panobinostat in combination with bortezomib and dexamethasone in relapsed and bortezomib-refractory multiple myeloma (PANORAMA 2). ASH Annual Meeting Abstracts 2011;118:814.Google Scholar
Harrison, S. J., Quach, H., Link, E. et al. A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma. Blood 2011;118:6274–83.CrossRefGoogle ScholarPubMed
Demo, S. D., Kirk, C. J., Aujay, M. A. et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67:6383–91.CrossRefGoogle ScholarPubMed
Siegel, D. S., Martin, T., Wang, M. et al. A phase 2 study of single-agent carfilzomib (PX-171–003-A1) in patients with relapsed and refractory multiple myeloma. Blood 2012;120:2817–25.CrossRefGoogle ScholarPubMed
Vij, R., Wang, M., Kaufman, J. L. et al. An open-label, single-arm, phase 2 (PX-171–004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood 2012;119:5661–70.CrossRefGoogle ScholarPubMed
Hsi, E. D., Steinle, R., Balasa, B. et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin. Cancer Res. 2008;14:2775–84.CrossRefGoogle ScholarPubMed
Tai, Y. T., Dillon, M., Song, W. et al. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood 2008;112:1329–37.CrossRefGoogle ScholarPubMed
Zonder, J. A., Mohrbacher, A. F., Singhal, S. et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 2012;120:552–9.CrossRefGoogle ScholarPubMed
Jakubowiak, A. J., Benson, D. M., Bensinger, W. et al. Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/refractory multiple myeloma. J. Clin. Oncol. 2012;30:1960–5.CrossRefGoogle ScholarPubMed
Lonial, S., Vij, R., Harousseau, J. L. et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J. Clin. Oncol. 2012;30:1953–9.CrossRefGoogle ScholarPubMed
Richardson, P. G., Jagannath, S., Moreau, P. et al. A phase 2 study of elotuzumab (Elo) in combination with lenalidomide and low-dose dexamethasone (Ld) in patients (pts) with relapsed/refractory multiple myeloma (R/R MM): updated results. ASH Annual Meeting Abstracts 2012;120:202.Google Scholar
Hovenga, S., Daenen, S. M., de Wolf, J. T. et al. Combined thalidomide and cyclophosphamide treatment for refractory or relapsed multiple myeloma patients: a prospective phase II study. Ann. Hematol. 2005;84:311–16.CrossRefGoogle ScholarPubMed
Moehler, T. M., Neben, K., Benner, A. et al. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 2001;98:3846–8.CrossRefGoogle ScholarPubMed
Palumbo, A., Larocca, A., Genuardi, M. et al. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial. Haematologica 2010;95:1144–9.CrossRefGoogle ScholarPubMed
Offidani, M., Corvatta, L., Marconi, M. et al. Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter, phase II study. Haematologica 2006;91:133–6.Google ScholarPubMed
Srikanth, M., Davies, F. E., Wu, P. et al. Survival and outcome of blastoid variant myeloma following treatment with the novel thalidomide containing regime DT-PACE. Eur. J. Haematol. 2008;81:432–6.CrossRefGoogle ScholarPubMed
Lee, S. S., Suh, C., Kim, B. S. et al. Bortezomib, doxorubicin, and dexamethasone combination therapy followed by thalidomide and dexamethasone consolidation as a salvage treatment for relapsed or refractory multiple myeloma: analysis of efficacy and safety. Ann Hematol 2010;89:905–12.CrossRefGoogle ScholarPubMed
Moreau, P., Pylypenko, H., Grosicki, S. et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12:431–40.CrossRefGoogle ScholarPubMed
Garderet, L., Iacobelli, S., Moreau, P. et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005–04 randomized phase III trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J. Clin. Oncol. 2012;30:2475–82.CrossRefGoogle ScholarPubMed
Rodon, P., Hulin, C., Pegourie, B. et al. Bendamustine, bortezomib and dexamethasone (BVD) in elderly patients with multiple myeloma in first relapse: updated results of the Intergroupe Francophone Du Myelome (IFM) 2009–01 Trial. ASH Annual Meeting Abstracts 2012;120:4044.Google Scholar
Richardson, P. G., Jagannath, S., Jakubowiak, A. J. et al. Phase II trial of lenalidomide, bortezomib, and dexamethasone in patients (pts) with relapsed and relapsed/refractory multiple myeloma (MM): updated efficacy and safety data after >2 years of follow-up. ASH Annual Meeting Abstracts 2010;116:3049.Google Scholar
Lentzsch, S., O’Sullivan, A., Kennedy, R. et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with refractory or relapsed multiple myeloma is safe and highly effective: results of phase I/II open-label, dose escalation study. ASH Annual Meeting Abstracts 2011;118:304.Google Scholar
Shah, J. J., Orlowski, R. Z., Alexanian, R. et al. Phase I trial of the combination of lenalidomide, thalidomide and dexamethasone in relapsed/refractory multiple myeloma. ASH Annual Meeting Abstracts 2010;116:1948.Google Scholar
Niesvizky, R., Wang, L., Orlowski, R. Z. et al. Phase Ib multicenter dose escalation study of carfilzomib plus lenalidomide and low dose dexamethasone (CRd) in relapsed and refractory multiple myeloma (MM). ASH Annual Meeting Abstracts 2009;114:304.Google Scholar
Leleu, X., Attal, M., Arnulf, B. et al. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009–02. Blood 2013 (in press).CrossRefGoogle Scholar
Richardson, P. G., Siegel, D., Baz, R. et al. Phase I study of pomalidomide MTD, safety and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood 2012 (in press).Google Scholar

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