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Management of treatment-emergent peripheral neuropathy in multiple myeloma

Leukemia volume 26, pages 595–608 (2012)Cite this article

Abstract

Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions.

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References

  1. Dispenzieri A, Kyle RA . Neurological aspects of multiple myeloma and related disorders. Best Pract Res Clin Haematol 2005; 18: 673–688.

    Article  CAS  PubMed  Google Scholar 

  2. Ropper AH, Gorson KC . Neuropathies associated with paraproteinemia. N Engl J Med 1998; 338: 1601–1607.

    Article  CAS  PubMed  Google Scholar 

  3. Delforge M, Blade J, Dimopoulos MA, Facon T, Kropff M, Ludwig H et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol 2010; 11: 1086–1095.

    Article  CAS  PubMed  Google Scholar 

  4. Tariman JD, Love G, McCullagh E, Sandifer S . Peripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. Clin J Oncol Nurs 2008; 12: 29–36.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Richardson PG, Xie W, Mitsiades C, Chanan-Khan AA, Lonial S, Hassoun H et al. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlates of response and neuropathy. J Clin Oncol 2009; 27: 3518–3525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hausheer FH, Schilsky RL, Bain S, Berghorn EJ, Lieberman F . Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol 2006; 33: 15–49.

    Article  CAS  PubMed  Google Scholar 

  7. Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res 2010; 70: 1970–1980.

    Article  CAS  PubMed  Google Scholar 

  8. Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood 2008; 111: 2765–2775.

    Article  CAS  PubMed  Google Scholar 

  9. Silverman L, Csizmadia V, Brewer K, Simpson C, Alden C . Proteasome inhibitor associated neuropathy is mechanism based. Blood 2008; 112: 2646a (abstract 2646).

    Article  Google Scholar 

  10. Csizmadia V, Raczynski A, Csizmadia E, Fedyk ER, Rottman J, Alden CL . Effect of an experimental proteasome inhibitor on the cytoskeleton, cytosolic protein turnover, and induction in the neuronal cells in vitro. Neurotoxicology 2008; 29: 232–243.

    Article  CAS  PubMed  Google Scholar 

  11. Cavaletti G, Gilardini A, Canta A, Rigamonti L, Rodriguez-Menendez V, Ceresa C et al. Bortezomib-induced peripheral neurotoxicity: A neurophysiological and pathological study in the rat. Exp Neurol 2007; 204: 317–325.

    Article  CAS  PubMed  Google Scholar 

  12. Richardson PG, Bruna J, Amato AA, Udina E, Mitsiades CS, Wen PY et al. Bortezomib-associated peripheral neuropathy: relationship between clinical neurophysiologic evidence in previously untreated multiple myeloma patients and preclinical characterization in a mouse model. Blood 2009; 114: 1485a (abstract 3860).

    Article  Google Scholar 

  13. Bruna J, Udina E, Ale A, Vilches JJ, Vynckier A, Monbaliu J et al. Neurophysiological, histological and immunohistochemical characterization of bortezomib-induced neuropathy in mice. Exp Neurol 2010; 223: 599–608.

    Article  CAS  PubMed  Google Scholar 

  14. Arastu-Kapur S, Ball AJ, Anderl JL, Bennett MK, Kirk CJ . Neurodegeneration induced by bortezomib exposure in vitro occurs via proteasome independent mechanisms. Blood 2009; 114: 1116a (abstract 2859).

    Article  Google Scholar 

  15. Arastu-Kapur S, Anderl JL, Kraus M, Parlati F, Shenk KD, Lee SJ et al. Non-proteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer Res 2011; 17: 2734–2743.

    Article  CAS  PubMed  Google Scholar 

  16. Dick LR, Fleming PE . Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov Today 2010; 15: 243–249.

    Article  CAS  PubMed  Google Scholar 

  17. Poruchynsky MS, Sackett DL, Robey RW, Ward Y, Annunziata C, Fojo T . Proteasome inhibitors increase tubulin polymerization and stabilization in tissue culture cells: a possible mechanism contributing to peripheral neuropathy and cellular toxicity following proteasome inhibition. Cell Cycle 2008; 7: 940–949.

    Article  CAS  PubMed  Google Scholar 

  18. Giannini F, Volpi N, Rossi S, Passero S, Fimiani M, Cerase A . Thalidomide-induced neuropathy: a ganglionopathy? Neurology 2003; 60: 877–878.

    Article  CAS  PubMed  Google Scholar 

  19. Chaudhry V, Cornblath DR, Corse A, Freimer M, Simmons-O’Brien E, Vogelsang G . Thalidomide-induced neuropathy. Neurology 2002; 59: 1872–1875.

    Article  CAS  PubMed  Google Scholar 

  20. Yildirim ND, Ayer M, Kucukkaya RD, Alpay N, Mete O, Yenerel MN et al. Leukocytoclastic vasculitis due to thalidomide in multiple myeloma. Jpn J Clin Oncol 2007; 37: 704–707.

    Article  PubMed  Google Scholar 

  21. Silva A, Wang Q, Wang M, Ravula SK, Glass JD . Evidence for direct axonal toxicity in vincristine neuropathy. J Peripher Nerv Syst 2006; 11: 211–216.

    Article  CAS  PubMed  Google Scholar 

  22. Krarup-Hansen A, Helweg-Larsen S, Schmalbruch H, Rorth M, Krarup C . Neuronal involvement in cisplatin neuropathy: prospective clinical and neurophysiological studies. Brain 2007; 130: 1076–1088.

    Article  CAS  PubMed  Google Scholar 

  23. Millennium Pharmaceuticals Inc. VELCADE® (bortezomib) for Injection. Prescribing Information. Cambridge, MA, USA, 2011. Issued November 2011, Rev 12.

  24. Celgene Corporation. THALOMID (thalidomide) Capsules Prescribing Information. Summit, NJ, USA, 2010. http://www.thalomid.com/pdf/Thalomid_PI.pdf. February 2010.

  25. Mileshkin L, Stark R, Day B, Seymour JF, Zeldis JB, Prince HM . Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J Clin Oncol 2006; 24: 4507–4514.

    Article  CAS  PubMed  Google Scholar 

  26. Mileshkin L, Prince HM . The troublesome toxicity of peripheral neuropathy with thalidomide. Leuk Lymphoma 2006; 47: 2276–2279.

    Article  CAS  PubMed  Google Scholar 

  27. Pal PK . Clinical and electrophysiological studies in vincristine induced neuropathy. Electromyogr Clin Neurophysiol 1999; 39: 323–330.

    CAS  PubMed  Google Scholar 

  28. Hospira Inc. Vincristine Sulfate Injection Prescribing Information. Lake Forest, IL, USA, 2008. http://www.hospira.com/_docs/VinCRIStine-482805-PROMOWEB.pdf.

  29. Cavaletti G, Bogliun G, Marzorati L, Tredici G, Colombo N, Parma G et al. Long-term peripheral neurotoxicity of cisplatin in patients with successfully treated epithelial ovarian cancer. Anticancer Res 1994; 14: 1287–1292.

    CAS  PubMed  Google Scholar 

  30. Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R et al. Efficacy and safety of once weekly bortezomib in multiple myeloma patients. Blood 2010; 116: 4745–4753.

    Article  CAS  PubMed  Google Scholar 

  31. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M et al. 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. Lancet 2010; 376: 2075–2085.

    Article  CAS  PubMed  Google Scholar 

  32. Dimopoulos MA, Mateos MV, Richardson PG, Schlag R, Khuageva NK, Shpilberg O et al. Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol 2011; 86: 23–31.

    Article  CAS  PubMed  Google Scholar 

  33. Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010; 28: 4621–4629.

    Article  CAS  PubMed  Google Scholar 

  34. Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, de Paz R et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 2010; 11: 934–941.

    Article  CAS  PubMed  Google Scholar 

  35. Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 2010; 28: 5101–5109.

    Article  CAS  PubMed  Google Scholar 

  36. Rosinol L, Cibeira MT, Mateos MV, Martinez J, Oriol A, Teruel AI et al. A phase III PETHEMA/GEM study of induction therapy prior autologous stem cell transplantation (ASCT) in multiple myeloma: superiority of VTD (bortezomib/thalidomide/dexamethasone) over TD and VBMCP/VBAD plus bortezomib. Blood 2010; 116: 139a–140a (abstract 307).

    Article  Google Scholar 

  37. Sonneveld P, Schmidt-Wolf I, van der Holt B, el Jarrari L, Bertsch U, Salwender H et al. HOVON-65/GMMG-HD4 randomized phase III trial comparing bortezomib, doxorubicin, dexamethasone (PAD) vs VAD followed by high-dose melphalan (HDM) and maintenance with bortezomib or thalidomide in patients with newly diagnosed multiple myeloma (MM). Blood 2010; 116: 23a–24a (abstract 40).

    Article  Google Scholar 

  38. Zervas K, Mihou D, Katodritou E, Pouli A, Mitsouli CH, Anagnostopoulos A et al. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol 2007; 18: 1369–1375.

    Article  CAS  PubMed  Google Scholar 

  39. Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A 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: 3892–3901.

    Article  CAS  PubMed  Google Scholar 

  40. Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment prior to autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood 2011; 118: 5752–5758.

    Article  CAS  PubMed  Google Scholar 

  41. Mikhael JR, Belch AR, Prince HM, Lucio MN, Maiolino A, Corso A et al. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Br J Haematol 2009; 144: 169–175.

    Article  CAS  PubMed  Google Scholar 

  42. Richardson PG, Briemberg H, Jagannath S, Wen PY, Barlogie B, Berenson J et al. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 2006; 24: 3113–3120.

    Article  CAS  PubMed  Google Scholar 

  43. Richardson PG, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol 2009; 144: 895–903.

    Article  CAS  PubMed  Google Scholar 

  44. Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M 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: 431–440.

    Article  PubMed  Google Scholar 

  45. O’Connor OA, Stewart AK, Vallone M, Molineaux CJ, Kunkel LA, Gerecitano JF et al. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res 2009; 15: 7085–7091.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Jagannath S, Vij R, Kaufman JL, Martin T, Niesvizky R, Gabrail NY et al. Long-term treatment and tolerability of the novel proteasome inhibitor carfilzomib (CFZ) in patients with relapsed and/or refractory multiple myeloma (R/R MM). Blood 2010; 116: 814a (abstract 1953).

    Article  Google Scholar 

  47. Martin T, Singhal SB, Wang M, Stewart AK, Jagannath S, Lonial S et al. Baseline peripheral neuropathy does not impact the efficacy and tolerability of the novel proteasome inhibitor carfilzomib (CFZ): results of a subset analysis of a phase 2 trial in patients with relapsed and refractory multiple myeloma (R/R MM). Blood 2010; 116: 1249a–1250a (abstract 3031).

    Article  Google Scholar 

  48. Papadopoulos K, Siegel DS, Singhal SB, Infante JR, Sausville EA, Gordon MS et al. Phase 1b evaluation of the safety and efficacy of a 30-minute IV infusion of carfilzomib in patients with relapsed and/or refractory multiple myeloma. Blood 2010; 116: 1245a–1246a (abstract 3024).

    Article  Google Scholar 

  49. Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Jagannath S et al. Results of PX-171-003-A1, an open-label, single-arm, phase 2 (ph 2) study of carfilzomib (CFZ) in patients (pts) with relapsed and refractory multiple myeloma (MM). Blood 2010; 116: 433a (abstract 985).

    Article  Google Scholar 

  50. Jakubowiak AJ, Dytfeld D, Jagannath S, Vesole DH, Anderson TB, Nordgren BK et al. Carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma: initial results of phase I/II MMRC trial. Blood 2010; 116: 376a–377a (abstract 862).

    Article  Google Scholar 

  51. Hamlin PA, Aghajanian C, Younes A, Hong DS, Palladino MA, Longenecker AM et al. First-in-human phase I study of the novel structure proteasome inhibitor NPI-0052. J Clin Oncol 2009; 27: 3516a (abstract 3516).

    Article  Google Scholar 

  52. Richardson P, Hofmeister C, Jakubowiak A, Zimmerman TM, Spear MA, Palladino MA et al. Phase 1 clinical trial of the novel structure proteasome inhibitor NPI-0052 in patients with relapsed and relapsed/refractory multiple myeloma (MM). Blood 2009; 114: 179a (abstract 431).

    Article  Google Scholar 

  53. Spencer A, Millward M, Mainwaring P, Harrison S, Catley L, Townsend A et al. Phase 1 clinical trial of the novel structure proteasome inhibitor NPI-0052. Blood 2009; 114: 1053a–1054a (abstract 2693).

    Google Scholar 

  54. Tosi P, Zamagni E, Cellini C, Plasmati R, Cangini D, Tacchetti P et al. Neurological toxicity of long-term (>1yr) thalidomide therapy in patients with multiple myeloma. Eur J Haematol 2005; 74: 212–216.

    Article  CAS  PubMed  Google Scholar 

  55. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007; 370: 1209–1218.

    Article  CAS  PubMed  Google Scholar 

  56. Lokhorst HM, Schmidt-Wolf I, Sonneveld P, van der Holt B, Martin H, Barge R et al. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma. Haematologica 2008; 93: 124–127.

    Article  CAS  PubMed  Google Scholar 

  57. Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006; 367: 825–831.

    Article  CAS  PubMed  Google Scholar 

  58. Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 2008; 112: 3107–3114.

    Article  CAS  PubMed  Google Scholar 

  59. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR . 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 2006; 24: 431–436.

    Article  CAS  PubMed  Google Scholar 

  60. Rajkumar SV, Rosinol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 2008; 26: 2171–2177.

    Article  CAS  PubMed  Google Scholar 

  61. Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 2009; 27: 3664–3670.

    Article  CAS  PubMed  Google Scholar 

  62. Glasmacher A, Hahn C, Hoffmann F, Naumann R, Goldschmidt H, von Lilienfeld-Toal M 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: 584–593.

    Article  CAS  PubMed  Google Scholar 

  63. von Lilienfeld-Toal M, Hahn-Ast C, Furkert K, Hoffmann F, Naumann R, Bargou R 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: 247–252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007; 357: 2123–2132.

    Article  CAS  PubMed  Google Scholar 

  65. Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N 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: 4459–4465.

    Article  CAS  PubMed  Google Scholar 

  66. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106: 4050–4053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006; 108: 3458–3464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357: 2133–2142.

    Article  CAS  PubMed  Google Scholar 

  69. Gay F, Hayman SR, Lacy MQ, Buadi F, Gertz MA, Kumar S et al. Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients. Blood 2010; 115: 1343–1350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 2010; 11: 29–37.

    Article  CAS  PubMed  Google Scholar 

  71. Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore Sr DF, Whittenberger BF et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood 2010; 116: 5838–5841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia 2010; 24: 1934–1939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Sullivan D et al. A phase 1/2 multi-center, randomized, open label dose escalation study to determine the maximum tolerated dose, safety, and efficacy of pomalidomide alone or in combination with low-dose dexamethasone in patients with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide and bortezomib. Blood 2010; 116: 377a–378a (abstract 864).

    Article  Google Scholar 

  74. Dimopoulos MA, Pouli A, Zervas K, Grigoraki V, Symeonidis A, Repoussis P et al. Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma. Ann Oncol 2003; 14: 1039–1044.

    Article  CAS  PubMed  Google Scholar 

  75. Sonneveld P, Suciu S, Weijermans P, Beksac M, Neuwirtova R, Solbu G et al. Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC-HOVON randomized phase III study (06914). Br J Haematol 2001; 115: 895–902.

    Article  CAS  PubMed  Google Scholar 

  76. Oken MM, Harrington DP, Abramson N, Kyle RA, Knospe W, Glick JH . Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479. Cancer 1997; 79: 1561–1567.

    Article  CAS  PubMed  Google Scholar 

  77. Pineda-Roman M, Zangari M, van Rhee F, Anaissie E, Szymonifka J, Hoering A et al. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma. Leukemia 2008; 22: 1419–1427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V et al. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood 2007; 109: 2767–2772.

    Article  CAS  PubMed  Google Scholar 

  79. Chaudhry V, Cornblath DR, Polydefkis M, Ferguson A, Borrello I . Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst 2008; 13: 275–282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ghosh N, Ferguson A, Ye X, Huff CA, Borrello IM . Bortezomib and thalidomide, a steroid free regimen in newly diagnosed patients with multiple myeloma. Blood 2009; 114: 1119a (abstract 2867).

    Article  Google Scholar 

  81. Anderson KC, Jagannath S, Jakubowiak A, Lonial S, Raje N, Alsina M et al. Lenalidomide, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma (MM): Encouraging outcomes and tolerability in a phase II study. J Clin Oncol 2009; 27: 442s (abstract 8536).

    Google Scholar 

  82. Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010; 116: 679–686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kumar S, Flinn IW, Richardson PG, Hari P, Callander NS, Noga SJ et al. Novel three- and four-drug combination regimens of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide, for previously untreated multiple myeloma: results from the multi-center, randomized, phase 2 EVOLUTION study. Blood 2010; 116: 273a (abstract 621).

    Article  Google Scholar 

  84. Richardson PG, Chanan-Khan AA, Lonial S, Krishnan AY, Carroll MP, Albitar M et al. Tanespimycin + bortezomib demonstrates safety, activity, and effective target inhibition in relapsed/refractory myeloma patients: updated results of a phase 1/2 study. Blood 2009; 114: 1128a–1129a (abstract 2890).

    Article  Google Scholar 

  85. Siegel DS, Krishnan A, Lonial S, Chatta G, Alsina M, Jagannath S et al. Phase II trial of SCIO-469 as monotherapy (M) or in combination with bortezomib (MB) in relapsed refractory multiple myeloma (MM). Blood 2006; 108: 1022a (abstract 3580).

    Article  Google Scholar 

  86. Siegel D, Jagannath S, Lonial S, Dimopoulos MA, Graef T, Pietrangelo D et al. Update on the phase IIb, open-label study of vorinostat in combination with bortezomib in patients with relapsed and refractory multiple myeloma. Blood 2009; 114: 1497a (abstract 3890).

    Article  Google Scholar 

  87. San Miguel JF, Sezer O, Siegel D, Guenther A, Mateos MV, Prosser I et al. A phase Ib, multi-center, open-label dose-escalation study of oral panobinostat (LBH589) and i.v. bortezomib in patients with relapsed multiple myeloma. Blood 2009; 114: 1481a–1482a (abstract 3852).

    Article  Google Scholar 

  88. Badros AZ, Richardson PG, Albitar M, Jagannath S, Tarantolo S, Wolf JL et al. Tanespimycin + bortezomib in relapsed/refractory myeloma patients: results from the Time-2 study. Blood 2009; 114: 742a–743a (abstract 1871).

    Google Scholar 

  89. Voorhees PM, Gasparetto C, Richards KL, Garcia R, Strader JS, Ferraro M et al. Vorinostat in combination with pegylated liposomal doxorubicin and bortezomib for patients with relapsed/refractory multiple myeloma: results of a phase I study. Blood 2009; 114: 129a–130a (abstract 306).

    Article  Google Scholar 

  90. Hrusovsky I, Emmerich B, von RA, Voegeli J, Taverna C, Olie RA et al. Bortezomib retreatment in relapsed multiple myeloma - results from a retrospective multicentre survey in Germany and Switzerland. Oncology 2010; 79: 247–254.

    Article  CAS  PubMed  Google Scholar 

  91. Petrucci MT, Blau IW, Corradini P, Dimopoulos MA, Drach J, Giraldo P et al. Efficacy and safety of retreatment with bortezomib in patients with multiple myeloma: interim results from RETRIEVE, a prospective international phase 2 study. Blood 2009; 114: 1487a–1488a (abstract 3866).

    Article  Google Scholar 

  92. Berenson JR, Jagannath S, Barlogie B, Siegel DT, Alexanian R, Richardson PG et al. Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma. Cancer 2005; 104: 2141–2148.

    Article  CAS  PubMed  Google Scholar 

  93. Wolf J, Richardson PG, Schuster M, LeBlanc A, Walters IB, Battleman DS . Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series. Clin Adv Hematol Oncol 2008; 6: 755–760.

    PubMed  Google Scholar 

  94. Popat R, Oakervee HE, Hallam S, Curry N, Odeh L, Foot N et al. Bortezomib, doxorubicin and dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term follow-up. Br J Haematol 2008; 141: 512–516.

    Article  CAS  PubMed  Google Scholar 

  95. Ghobrial IM, Weller E, Vij R, Munshi NC, Banwait R, Bagshaw M et al. Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study. Lancet Oncol 2011; 12: 263–272.

    Article  CAS  PubMed  Google Scholar 

  96. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Laumann K et al. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood 2010; 115: 3416–3417.

    Article  CAS  PubMed  Google Scholar 

  97. Plasmati R, Pastorelli F, Cavo M, Petracci E, Zamagni E, Tosi P et al. Neuropathy in multiple myeloma treated with thalidomide: a prospective study. Neurology 2007; 69: 573–581.

    Article  CAS  PubMed  Google Scholar 

  98. Cavo M, Di RF, Zamagni E, Patriarca F, Tacchetti P, Casulli AF et al. Short-term thalidomide incorporated into double autologous stem-cell transplantation improves outcomes in comparison with double autotransplantation for multiple myeloma. J Clin Oncol 2009; 27: 5001–5007.

    Article  CAS  PubMed  Google Scholar 

  99. Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021–1030.

    Article  CAS  PubMed  Google Scholar 

  100. Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y et al. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol 2010; 11: 1057–1065.

    Article  CAS  PubMed  Google Scholar 

  101. Favis R, Sun Y, van de Velde H, Broderick E, Levey L, Meyers M et al. Genetic variation associated with bortezomib-induced peripheral neuropathy. Pharmacogenet Genomics 2011; 21: 121–129.

    Article  CAS  PubMed  Google Scholar 

  102. Johnson DC, Corthals SL, Walker BA, Ross FM, Gregory WM, Dickens NJ et al. Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma. J Clin Oncol 2011; 29: 797–804.

    Article  CAS  PubMed  Google Scholar 

  103. Calhoun EA, Fishman DA, Roland PY, Lurain JR, Chang C, Cella D . Validity and selective sensitivity of the FACT-GOG Ntx. J Clin Oncol 2000; 19: 446a (abstract 1751).

    Google Scholar 

  104. Cavaletti G, Frigeni B, Lanzani F, Piatti M, Rota S, Briani C et al. The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute-Common Toxicity Scale. J Peripher Nerv Syst 2007; 12: 210–215.

    Article  PubMed  Google Scholar 

  105. Postma TJ, Aaronson NK, Heimans JJ, Muller MJ, Hildebrand JG, Delattre JY et al. The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer 2005; 41: 1135–1139.

    Article  CAS  PubMed  Google Scholar 

  106. CI-PERINOMS study group. CI-PERINOMS: chemotherapy-induced peripheral neuropathy outcome measures study. J Peripher Nerv Syst 2009; 14: 69–71.

    Article  Google Scholar 

  107. Hauser K, Walsh D . Visual analogue scales and assessment of quality of life in cancer. J Support Oncol 2008; 6: 277–282.

    PubMed  Google Scholar 

  108. Velasco R, Petit J, Clapes V, Verdu E, Navarro X, Bruna J . Neurological monitoring reduces the incidence of bortezomib-induced peripheral neuropathy in multiple myeloma patients. J Peripher Nerv Syst 2010; 15: 17–25.

    Article  CAS  PubMed  Google Scholar 

  109. Laaksonen S, Remes K, Koskela K, Voipio-Pulkki LM, Falck B . Thalidomide therapy and polyneuropathy in myeloma patients. Electromyogr Clin Neurophysiol 2005; 45: 75–86.

    CAS  PubMed  Google Scholar 

  110. De Grandis D . Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review. CNS Drugs 2007; 21: 39–43.

    Article  CAS  PubMed  Google Scholar 

  111. Gedlicka C, Scheithauer W, Schull B, Kornek GV . Effective treatment of oxaliplatin-induced cumulative polyneuropathy with alpha-lipoic acid. J Clin Oncol 2002; 20: 3359–3361.

    Article  CAS  PubMed  Google Scholar 

  112. Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier KS et al. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support Care Cancer 2011; 19: 833–841.

    Article  PubMed  Google Scholar 

  113. Durand JP, Deplanque G, Gorent J, Montheil V, Raymond E, Scotte F et al. Efficacy of venlafaxine for the prevention and relief of acute neurotoxicity of oxaliplatin: Results of EFFOX, a randomized, double-blinded, placebo-controlled prospective study. J Clin Oncol 2009; 27: 9533 (abstract 9533).

    Article  Google Scholar 

  114. Colvin LA, Johnson PR, Mitchell R, Fleetwood-Walker SM, Fallon M . From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol. J Clin Oncol 2008; 26: 4519–4520.

    Article  PubMed  Google Scholar 

  115. Sima L, Yin C . Efficacy of electroacupuncture for bone metastatic cancer patients with neuropathic pain: a randomized controlled trial. J Clin Oncol 2009; 27: 9534 (abstract 9534).

    Article  Google Scholar 

  116. Badros A, Goloubeva O, Dalal JS, Can I, Thompson J, Rapoport AP et al. Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer 2007; 110: 1042–1049.

    Article  CAS  PubMed  Google Scholar 

  117. Mohty B, El-Cheikh J, Yakoub-Agha I, Moreau P, Harousseau JL, Mohty M . Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations. Haematologica 2010; 95: 311–319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Palumbo A, Facon T, Sonneveld P, Blade J, Offidani M, Gay F et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood 2008; 111: 3968–3977.

    Article  CAS  PubMed  Google Scholar 

  119. Ludwig H, Hajek R, Tothova E, Drach J, Adam Z, Labar B et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009; 113: 3435–3442.

    Article  CAS  PubMed  Google Scholar 

  120. Palumbo A, Delforge M, Catalano J, Hajek R, Kropff M, Petrucci MT et al. A phase 3 study evaluating the efficacy and safety of lenalidomide combined with melphalan and prednisone in patients 65 years with newly diagnosed multiple myeloma (NDMM): continuous use of lenalidomide vs fixed-duration regimens. Blood 2010; 116: 273a–274a (abstract 622).

    Article  Google Scholar 

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Acknowledgements

Administrative assistance was provided in part by Katie Redman and Jane Saunders during the development of this publication, who were supported in part by the Rick Corman Multiple Myeloma Research Fund and by an unrestricted grant from Millennium Pharmaceuticals, Inc., respectively. All authors were fully responsible for the writing, content and final approval of the manuscript.

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Author notes

  1. P G Richardson, M Delforge, M Beksac, P Wen, J L Jongen, O Sezer, E Terpos, N Munshi, A Palumbo, S V Rajkumar, J L Harousseau, P Moreau, H Avet-Loiseau, J H Lee, M Cavo, G Merlini, P Voorhees, W J Chng, A Mazumder, S Usmani, H Einsele, R Comenzo, R Orlowski, D Vesole, J J Lahuerta, R Niesvizky, D Siegel, M-V Mateos, M Dimopoulos, S Lonial, S Jagannath, J Bladé, J San Miguel, G Morgan, K C Anderson, B G M Durie and P Sonneveld: All members of the International Myeloma Working Group are listed in the online-only Supplementary Information.

Authors and Affiliations

  1. Dana-Farber Cancer Institute, Boston, MA, USA

    P G Richardson, P Wen, N Munshi & K C Anderson

  2. University Hospital Leuven, Leuven, Belgium

    M Delforge

  3. Ankara University, Ibn-i Sina Hospital, Ankara, Turkey

    M Beksac

  4. Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands

    J L Jongen & P Sonneveld

  5. University Medical Center, Hamburg, Germany

    O Sezer

  6. School of Medicine, University of Athens, Athens, Greece

    E Terpos & M Dimopoulos

  7. University of Torino, Torino, Italy

    A Palumbo

  8. Mayo Clinic, Rochester, MN, USA

    S V Rajkumar

  9. Intergroupe Francophone du Myélome, Nantes, France

    J L Harousseau, P Moreau & H Avet-Loiseau

  10. Gachon University GIL Hospital, Incheon, Korea

    J H Lee

  11. Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy

    M Cavo

  12. Amyloidosis Research and Treatment Center, University of Pavia, Pavia, Italy

    G Merlini

  13. The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA

    P Voorhees

  14. Department of Haematology and Oncology, National University Health System, Singapore, Singapore

    W J Chng

  15. New York University School of Medicine, New York, NY, USA

    A Mazumder

  16. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    S Usmani

  17. University of Wurzburg, Wurzburg, Germany

    H Einsele

  18. Tufts Medical Center, Boston, MA, USA

    R Comenzo

  19. Department of Lymphoma and Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    R Orlowski

  20. Hackensack University Medical Center, Hackensack, NJ, USA

    D Vesole & D Siegel

  21. PETHEMA, Hospital Universitario 12 de Octubre, Madrid, Spain

    J J Lahuerta

  22. Center of Excellence for Lymphoma and Myeloma, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA

    R Niesvizky

  23. Hospital Universitario Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain

    M-V Mateos & J San Miguel

  24. Winship Cancer Institute of Emory University, Atlanta, GA, USA

    S Lonial

  25. Mount Sinai Hospital, New York, NY, USA

    S Jagannath

  26. Institute of Hematology and Oncology, Institut d’Investigacions Biomèdiques August Pi I Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain

    J Bladé

  27. Royal Marsden Hospital, London, UK

    G Morgan

  28. Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA, USA

    B G M Durie

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  1. P G Richardson
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on behalf of the International Myeloma Working Group

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Correspondence to P G Richardson.

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Competing interests

Paul G Richardson is an advisor for Millennium Pharmaceuticals, Celgene Corporation, Novartis Pharmaceuticals, Johnson & Johnson and Bristol Myers Squibb. Michel Delforge is a consultant for Janssen and Celgene. He has also received speaker’s honoraria from these companies. Joost L Jongen has received personal compensation from Pfizer. Orhan Sezer has received honoraria from Amgen, Celgene, Janssen and Novartis. Dr Sezer has also received research funding from Janssen and Novartis. Antonio Palumbo has received honoraria from Celgene, Janssen-Cilag, Merck and Amgen, and is on an advisory committee for Celgene and Janssen-Cilag. Shaji Kumar has received research funding from Celgene, Millennium and Novartis. He is a consultant for Merck. Philippe Moreau has received honoraria from Celgene, Janssen and Millennium. Michele Cavo has received honoraria from Janssen, Celgene and Millennium. Peter Voorhees is on speaker bureaus for Celgene and Millennium. Wee Joo Chng has received honoraria from Janssen, Celgene and Novartis, and has received research funding from Janssen and Roche. Amitabha Mazumder is a consultant for Celgene and Millennium, and has also received honoraria from these companies. Hermann Einsele is on the speaker bureaus for Celgene, Novartis and Janssen-Cilag. Raymond Comenzo is a scientific advisor for Millennium and Onyx, and also a consultant for Neotope and Millennium. He has received research support from Celgene and Millennium. Robert Orlowski has received research funding from Celgene, Millennium and Johnson and Johnson. He is also on advisory boards for Celgene, Millennium, Centocor, Novartis, Cephalon and Onyx, and has received honoraria from these companies. Juan José Lahuerta has received honoraria from Celgene and Janssen-Cilag. Ruben Niesvizky is a speaker and consultant for Celgene, Millennium, Onyx and Novartis. He has also received research support from these companies. David Siegel is on speaker bureaus for Celgene and Millennium. Maria-Victoria Mateos has received honoraria from Janssen, Celgene, Millennium and Novartis. Meletios Dimopoulos has received honoraria from Celgene, Ortho-Biotech and Millennium. Sagar Lonial is a consultant for Millennium, Celgene, Novartis, BMS, Merck and Onyx. Joan Bladé has received honoraria for lectures from Celgene and Jansen Cilag. He is also on advisory boards for these companies and has received grant support from the same. Jésus San Miguel is on advisory boards for Millennium, Janssen-Cilag and Celgene. Kenneth C Anderson is on advisory boards for Celgene, Millennium, Ony, BMS, Merck and Novartis. He is also the founder of Acetylon. Brian GM Durie is on advisory boards for Millennium, Celgene and Onyx. Pieter Sonneveld is on advisory boards for Janssen, Celgene, Onyx, Novartis and Millennium-Takeda. He has also received research support from Celgene and Janssen. The remaining authors declare no conflict of interest.

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Richardson, P., Delforge, M., Beksac, M. et al. Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia 26, 595–608 (2012). https://doi.org/10.1038/leu.2011.346

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