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Lenalidomide in Myeloma

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Opinion statement

The standard treatment approach to symptomatic myeloma consists of induction therapy, consolidation with high-dose chemotherapy and autologous hematopoietic stem cell transplantation in appropriate patients, maintenance therapy, and salvage therapy. Salvage therapy is of particular importance because not all patients respond to primary therapy, and relapse is virtually universal in responding patients. Newer agents such as thalidomide, bortezomib, and lenalidomide are very active in patients with relapsed or refractory disease. Their use singly and in combination results in excellent cytoreduction including complete remissions in patients relapsing – even after extensive prior therapy. These novel agents have been usually used as salvage therapy in patients relapsing after standard treatment options including transplantation; a setting in which they are thought to improve survival. However, there is an increasing trend to start using them early in the course of the disease; for induction therapy. While early deployment of these agents is certainly associated with high-response rates, evidence that this improves long-term outcome (survival) in patients who subsequently undergo intensive therapy and transplantation is lacking. Toxicity, expense, and possible long-term consequences on the biology of the disease (for example, development of refractory relapse) remain a concern. The most appropriate use of newer agents such as lenalidomide is as salvage therapy of relapsed or refractory disease, and their use as part of induction therapy should be confined to clinical trials until additional data and long-term follow-up are available.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. Singhal S, Mehta J (2006) Multiple myeloma. Clin J Am Soc Nephrol 1:1322–1330

    Article  PubMed  CAS  Google Scholar 

A recent review article discussing all aspects of myeloma management in depth.

  1. Durie BGM, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M, Child JA, Comenzo R, Djulbegovic B, Fantl D, Gahrton G, Harousseau JL, Hungria V, Joshua D, Ludwig H, Mehta J, Morales AR, Morgan G, Nouel A, Oken M, Powles R, Roodman D, San Miguel J, Shimizu K, Singhal S, Sirohi B, Sonneveld P, Tricot G, Van Ness B (2003) Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 4:379–398

    Article  PubMed  Google Scholar 

  2. Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M (2006) Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 367:825–831

    Article  PubMed  CAS  Google Scholar 

  3. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR (2006) Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 24:431–436

    Article  PubMed  CAS  Google Scholar 

  4. Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, Fassas A, Zangari M, Hollmig K, Pineda-Roman M, Lee C, Talamo G, Thertulien R, Kiwan E, Krishna S, Fox M, Crowley J (2006) Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 354:1021–1030

    Article  PubMed  CAS  Google Scholar 

  5. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R (1996) A prospective, randomized trial of autologous bone marrow transplantation versus conventional chemotherapy in multiple myeloma. N Engl J Med 335:91–97

    Article  PubMed  CAS  Google Scholar 

  6. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ (2003) High dose therapy improves the outcome of patients with multiple myeloma: The MRC Myeloma VII randomized trial. N Engl J Med 348:1875–1883

    Article  PubMed  CAS  Google Scholar 

  7. Bladé J, Rosiñol L, Sureda A, Ribera JM, Díaz-Mediavilla J, García-Laraña J, Mateos MV, Palomera L, Fernandez-Calvo J, Marti JM, Giraldo P, Carbonell F, Callis M, Trujillo J, Gardella S, Moro MJ, Barez A, Soler A, Font L, Fontanillas M, San Miguel J (2005) High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood 106:3755–3759

    Article  PubMed  Google Scholar 

  8. Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, Macro M, Pertuiset E, Dreyfus F, Mariette X, Boccacio C, Brouet JC (1998) High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 92:3131–3136

    PubMed  CAS  Google Scholar 

  9. Singhal S, Powles R, Sirohi B, Treleaven J, Kulkarni S, Mehta J (2002) Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma. Bone Marrow Transplant 30:673–679

    Article  PubMed  CAS  Google Scholar 

  10. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–502

    Article  PubMed  CAS  Google Scholar 

  11. Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J (1999) Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 93:55–65

    PubMed  CAS  Google Scholar 

  12. Barlogie B, Tricot GJ, van Rhee F, Angtuaco E, Walker R, Epstein J, Shaughnessy JD, Jagannath S, Bolejack V, Gurley J, Hoering A, Vesole D, Desikan R, Siegel D, Mehta J, Singhal S, Munshi NC, Dhodapkar M, Jenkins B, Attal M, Harousseau JL, Crowley J (2006) Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 135:158–164

    Article  PubMed  Google Scholar 

  13. Mehta J, Singhal S (1998) Graft-versus-myeloma. Bone Marrow Transplant 22:835–843

    Article  PubMed  CAS  Google Scholar 

  14. Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM, Barlogie B, Salmon SE (2002) Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 99:3163–3168

    Article  PubMed  CAS  Google Scholar 

  15. Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yacoub-Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T (2006) Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 108:3289–3294

    Article  PubMed  CAS  Google Scholar 

  16. Singhal S, Mehta J (2003) Treatment of relapsed and refractory multiple myeloma. Curr Treatment Options Oncol 4:229–237

    Article  Google Scholar 

  17. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341:1565–1571

    Article  PubMed  CAS  Google Scholar 

  18. Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N, Badros A, Zangari M, Anaissie E, Epstein J, Shaughnessy J, Ayers D, Spoon D, Tricot G (2001) 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 98:492–494

    Article  PubMed  CAS  Google Scholar 

  19. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609–2617

    Article  PubMed  CAS  Google Scholar 

  20. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Blade J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498

    Article  PubMed  CAS  Google Scholar 

  21. Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F, LeBlanc R, Catley LP, Doss D, Kelly K, McKenney M, Mechlowicz J, Freeman A, Deocampo R, Rich R, Ryoo JJ, Chauhan D, Balinski K, Zeldis J, Anderson KC (2002) Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 100:3063–3067

    Article  PubMed  CAS  Google Scholar 

Phase I study of lenalidomide showing activity of the drug at various does and dose-related myelosuppression.

  1. Dimopoulos MA, Spencer A, Attal M, Prince M, Harousseau JL, Dmoszynska A: Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma: results of a phase 3 study (MM-010) [ASH Annual Meeting Abstracts]. Blood 2005, 106:6.

  2. Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, Patterson RT, Stirling DI, Kaplan G (1999) Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-a. J Immunol 163:380–386

    PubMed  CAS  Google Scholar 

  3. Muller GW, Chen R, Huang SY, Corral LG, Wong LM, Patterson RT, Chen Y, Kaplan G, Stirling DI (1999) Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett 9:1625–1630

    Article  PubMed  CAS  Google Scholar 

  4. Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, Treon SP, Lin B, Schlossman RL, Richardson P, Muller G, Stirling DI, Anderson KC (2000) Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 96:2943–2950

    PubMed  CAS  Google Scholar 

  5. Davies FE, Raje N, Hideshima T, Lentzsch S, Young G, Tai YT, Lin B, Podar K, Gupta D, Chauhan D, Treon SP, Richardson PG, Schlossman RL, Morgan GJ, Muller GW, Stirling DI, Anderson KC (2001) Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 98:210–216

    Article  PubMed  CAS  Google Scholar 

  6. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, Munshi NC, Treon SP, Anderson KC (2002) Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 99:4525–4530

    Article  PubMed  CAS  Google Scholar 

  7. Zangari M, Tricot G, Zeldis J, Eddlemon P, Saghafifar F, Barlogie B: Results of a phase I study of CC-013 for the treatment of multiple myeloma patients who relapse after high dose chemotherapy (HDCT) [ASH Annual Meeting Abstracts]. Blood 2001, 98:775a.

    Google Scholar 

  8. Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K, Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC (2006) A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108:3458–3464

    Article  PubMed  CAS  Google Scholar 

  9. Richardson P, Jagannath S, Hussein M, Berenson J, Singhal S, Irwin D, Williams SF, Bensinger W, Badros AZ, Vescio R, Kenvin L, Yu Z, Olesnyckyj M, Faleck H, Zeldis J, Knight R, Anderson KC: A multicenter, single-arm, open-label study to evaluate the efficacy and safety of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma; preliminary results [ASH Annual Meeting Abstracts]. Blood 2005, 106:1565.

  10. Weber D, Wang M, Chen C, Belch A, Stadtmauer EA, Niesvisky R, Yu Z, Olesnyckyj M, Zeldis J, Knight RD, Dimopoulos M: Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): results of 2 phase III studies (MM-009, MM-010) and subgroup analysis of patients with impaired renal function [ASH Annual Meeting Abstracts]. Blood 2006, 108:3547.

    Google Scholar 

  11. Chanan-Khan AA, Weber D, Dimopoulos M, Chen C, Niesvizky R, Wang M, Belch A, Attal M, Spencer A, Prince M, Olesnyckyj M, Zeldis J, Yu Z, Knight R: Lenalidomide (L) in combination with dexamethasone (D) improves survival and time to progression in elderly patients (pts) with relapsed or refractory (rel/ref) multiple myeloma (MM) [ASH Annual Meeting Abstracts]. Blood 2006, 108:3551.

    Google Scholar 

  12. Wang M, Knight R, Dimopoulos M, Siegel D, Rajkumar SV, Facon T, Alexanian R, Yu Z, Zeldis J, Olesnyckyj M, Weber D: Lenalidomide in combination with dexamethasone was more effective than dexamethasone in patients who have received prior thalidomide for relapsed or refractory multiple myeloma [ASH Annual Meeting Abstracts]. Blood 2006, 108:3553.

    Google Scholar 

  13. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, Zeldenrust SR, Kumar S, Greipp PR, Fonseca R, Lust JA, Russell SJ, Kyle RA, Witzig TE, Gertz MA (2005) Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106:4050–4053

    Article  PubMed  CAS  Google Scholar 

A study showing the powerful activity of lenalidomide withdexamethasone in patients with previously-untreated myeloma.

  1. Lacy M, Gertz M, Dispenzieri A, Hayman S, Geyer S, Zeldenrust S, Kumar S, Greipp P, Fonseca R, Lust J, Russell S, Kyle R, Witzig T, Bergsagel L, Rajkumar SV: Lenalidomide plus dexamethasone (Rev/Dex) in newly diagnosed myeloma: response to therapy, time to progression, and survival [ASH Annual Meeting Abstracts]. Blood 2006, 108:798.

    Google Scholar 

  2. Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Greipp P: A randomized phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group [ASH Annual Meeting Abstracts]. Blood 2006, 108:799.

  3. Baz R, Walker E, Karam M, Choueiri T, Jawde R, Bruening K, Reed J, Faiman B, Ellis Y, Brand C, Srkalovic G, Andresen S, Knight R, Zeldis J, Hussein M (2006) Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol 17:1766–1771

    Article  PubMed  CAS  Google Scholar 

  4. Richardson PG, Jagannath S, Avigan DE, Alsina M, Schlossman RL, Mazumder A, Munshi NC, Ghobrial I, Doss D, McKenney ML, Farrell MG, Warren DL, Lunde LE, Gourley B, Vaccaro S, Delaney C, Pountney S, Mitsiades CS, Hideshima T, Byrne C, Knight R, Birner A, Myers T, Weller E, Anderson KC: lenalidomide plus bortezomib (Rev-Vel) in relapsed and/or refractory multiple myeloma (MM): final results of a multicenter phase 1 trial [ASH Annual Meeting Abstracts]. Blood 2006, 108:405.

  5. Knop S, Gerecke C, Topp MS, Liebisch P, Hess G, Kotkiewitz S, Einsele H, Bargou R: Lenalidomide (Revlimid), Adriamycin and dexamethasone chemotherapy (RAD) is safe and effective in treatment of relapsed multiple myeloma - first results of a German multicenter phase I/II trial [ASH Annual Meeting Abstracts]. Blood 2006, 108:408.

    Google Scholar 

  6. Palumbo A, Falco P, Falcone A, Corradini P, Di Raimondo F, Giuliani N, Rossi G, Morabito F, Canepa L, Gozzetti A, Ambrosini MT, Zeldis J, Knight R, Foà R, Boccadoro M, Petrucci MT: Oral Revlimid plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma: results of a multicenter phase I/II study [ASH Annual Meeting Abstracts]. Blood 2006, 108:800.

    Google Scholar 

  7. Sviggum HP, Davis MD, Rajkumar SV, Dispenzieri A (2006) Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma. Arch Dermatol 142:1298–1302

    Article  PubMed  CAS  Google Scholar 

  8. Bennett CL, Hussain Z, Courtney M, Yarnold P, Raisch D, McKoy JM: RADAR update on thalidomide (thal)- and lenalidomide (len)-associated venous thromboembolism (VTE): safety concerns persist for multiple myeloma (MM) despite FDA approvals in this setting [ASH Annual Meeting Abstracts]. Blood 2006, 108:3310.

  9. Niesvizky R, Jayabalan DS, Zafar F, Christos P, Lent R, Pearse R, Tepler J, Ely S, Shore T, Harpel J, Schuster M, Pekle K, Jalbrzikowski JB, Cho HJ, Leonard J, Mazumdar M, Chen-Kiang S, Coleman M: Lenalidomide induced myelosuppression is potentially associated with renal dysfunction in treatment naïve myeloma (MM) patients receiving BiRD (Biaxin/Revlimid/Dexamethasone) combination therapy (rx) [ASH Annual Meeting Abstracts]. Blood 2006, 108:3549.

    Google Scholar 

  10. http://www.celgene.com/About.aspx?S=8 (Accessed 20 January 2007).

  11. Rajkumar SV, Blood E (2006) Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 354:2079–2080

    Article  PubMed  Google Scholar 

  12. Knight R, DeLap RJ, Zeldis JB (2006) Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 354:2079–2080

    Article  PubMed  CAS  Google Scholar 

  13. http://www.celgene.com/PDF/RevlimidPI.pdf (Accessed 20 January 2007).

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Authors and Affiliations

  1. The Feinberg School of Medicine, The Robert H Lurie Comprehensive Cancer Center, Northwestern University, 676 N St Clair Street, Suite 850, Chicago, IL, 60611, USA

    Seema Singhal MD & Jayesh Mehta MD

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  1. Seema Singhal MD
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Correspondence to Seema Singhal MD.

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Disclosures: SS: Speaker bureaus of Celgene Corporation and Millennium Pharmaceuticals. JM: Speaker bureau of Celgene Corporation.

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Singhal, S., Mehta, J. Lenalidomide in Myeloma. Curr. Treat. Options in Oncol. 8, 154–163 (2007). https://doi.org/10.1007/s11864-007-0011-7

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