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A comparison of bortezomib, cyclophosphamide, and dexamethasone (Vel-CD) chemotherapy without and with thalidomide (Vel-CTD) for the treatment of relapsed or refractory multiple myeloma

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Abstract

We compared the clinical responses and toxicities between bortezomib-based salvage chemotherapy combined with cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) and without thalidomide (Vel-CD) in patients with relapsed or refractory MM. Eighty-six patients received at least two cycles of treatment with Vel-CTD (bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, and 11; cyclophosphamide 150 mg/m2 orally on days 1–4; thalidomide 50–100 mg/day orally every day; and dexamethasone 20 mg/m2 i.v. on days 1, 4, 8, and 11 every 3 weeks), and 67 patients were given at least two cycles of Vel-CD, which is the same regimen as Vel-CTD except without thalidomide. The overall response rates of the Vel-CD and Vel-CTD groups were 88% and 90% (p > 0.05), respectively. There was no difference in the progression free survival (p = 0.69) and overall survival rates (p = 0.49) between the two groups. Grade 3 or more adverse hematologic events occurred in the same proportion of patients in both groups. In terms of non-hematologic toxicities, the Vel-CTD group showed a higher proportion of autonomic neuropathy, motor neuropathy, and sensory neuropathy compared to the Vel-CD group (each, p < 0.05). Only three patients in the Vel-CTD group showed thrombotic events despite aspirin prophylaxis. The Vel-CD regimen in patients with relapsed or refractory MM is an effective and more tolerable salvage therapy compared to Vel-CTD in terms of its comparable response rate and less severe of non-hematologic toxicities.

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References

  1. Lee JH, Lee DS, Lee JJ, Chang YH, Jin JY, Jo DY, Bang SM, Kim HJ, Kim JS, Kim K, Eom HS, Min CK, Yoon SS, Kim SH, Suh C, Cho KS (2010) Multiple myeloma in Korea: past, present, and future perspectives. Experience of the Korean Multiple Myeloma Working Party. Int J Hematol 92:52–57

    Article  Google Scholar 

  2. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111:2516–2520

    Article  CAS  Google Scholar 

  3. 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  CAS  Google Scholar 

  4. Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Miguel JS, Blade J, Boccadoro M, Cavenagh J, Alsina M, Rajkumar SV, Lacy M, Jakubowiak A, Dalton W, Boral A, Esseltine DL, Schenkein D, Anderson KC (2007) Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 110:3557–3560

    Article  CAS  Google Scholar 

  5. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin DH, Rajkumar SV, Srkalovic G, Alsina M, Anderson KC (2006) Extended follow-up of a phase II trial in relapsed, refractory multiple myeloma: final time-to-event results from the SUMMIT trial. Cancer 106:1316–1319

    Article  CAS  Google Scholar 

  6. Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC (2004) A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 127:165–172

    Article  CAS  Google Scholar 

  7. Palumbo A, Avonto I, Bruno B, Ambrosini MT, Bringhen S, Cavallo F, Falco P, Boccadoro M (2006) Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma. Eur J Haematol 76:273–277

    Article  CAS  Google Scholar 

  8. Kyriakou C, Thomson K, D’Sa S, Flory A, Hanslip J, Goldstone AH, Yong KL (2005) 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 129:763–770

    Article  CAS  Google Scholar 

  9. Kropff MH, Lang N, Bisping G, Domine N, Innig G, Hentrich M, Mitterer M, Sudhoff T, Fenk R, Straka C, Heinecke A, Koch OM, Ostermann H, Berdel WE, Kienast J (2003) Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Br J Haematol 122:607–616

    Article  CAS  Google Scholar 

  10. Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL (2007) 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 25:3892–3901

    Article  CAS  Google Scholar 

  11. Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M, Dechow T, Kroger N, Salwender H, Metzner B, Sezer O, Engelhardt M, Wolf HH, Einsele H, Volpert S, Heinecke A, Berdel WE, Kienast J (2007) Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 138:330–337

    Article  CAS  Google Scholar 

  12. Berenson JR, Yang HH, Sadler K, Jarutirasarn SG, Vescio RA, Mapes R, Purner M, Lee SP, Wilson J, Morrison B, Adams J, Schenkein D, Swift R (2006) Phase I/II trial assessing bortezomib and melphalan combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. J Clin Oncol 24:937–944

    Article  CAS  Google Scholar 

  13. Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V, Cangialosi C, Caravita T, Morabito F, Musto P, Bringhen S, Falco P, Avonto I, Cavallo F, Boccadoro M (2007) Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood 109:2767–2772

    Article  CAS  Google Scholar 

  14. Reece DE, Rodriguez GP, Chen C, Trudel S, Kukreti V, Mikhael J, Pantoja M, Xu W, Stewart AK (2008) Phase I–II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. J Clin Oncol 26:4777–4783

    Article  CAS  Google Scholar 

  15. Kropff M, Liebisch P, Knop S, Weisel K, Wand H, Gann CN, Berdel WE, Einsele H (2009) DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myeloma. Ann Hematol 88:1125–1130

    Article  CAS  Google Scholar 

  16. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG, Zepeda VH, Mikhael JR, Leis JF, Bergsagel PL, Fonseca R, Stewart AK (2009) Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 23:1337–1341

    Article  CAS  Google Scholar 

  17. Bensinger WI, Jagannath S, Vescio R, Camacho E, Wolf J, Irwin D, Capo G, McKinley M, Potts P, Vesole DH, Mazumder A, Crowley J, Becker P, Hilger J, Durie BG (2010) Phase 2 study of two sequential three-drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma. Br J Haematol 148:562–568

    Article  CAS  Google Scholar 

  18. Davies FE, Wu P, Jenner M, Srikanth M, Saso R, Morgan GJ (2007) The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Haematologica 92:1149–1150

    Article  CAS  Google Scholar 

  19. Kim YK, Sohn SK, Lee JH, Yang DH, Moon JH, Ahn JS, Kim HJ, Lee JJ (2010) 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 89:475–482

    Article  CAS  Google Scholar 

  20. Badros A, Goloubeva O, Dalal JS, Can I, Thompson J, Rapoport AP, Heyman M, Akpek G, Fenton RG (2007) Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer 110:1042–1049

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Offidani M, Corvatta L, Polloni C, Gentili S, Mele A, Rizzi R, Catarini M, Caraffa P, Samori A, Blasi N, Ferranti M, Malerba L, Brunori M, Leoni P (2011) Thalidomide, dexamethasone, Doxil and Velcade (ThaDD-V) followed by consolidation/maintenance therapy in patients with relapsed-refractory multiple myeloma. Ann Hematol 90:1449–1456

    Article  CAS  Google Scholar 

  23. Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, Blade J, Richardson P, Orlowski R, Siegel D, Jagannath S, Facon T, Avet-Loiseau H, Lonial S, Palumbo A, Zonder J, Ludwig H, Vesole D, Sezer O, Munshi NC, San Miguel J (2011) Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 117:4691–4695

    Article  CAS  Google Scholar 

  24. Kim SJ, Kim K, Do YR, Bae SH, Yang DH, Lee JJ (2011) Low-dose acyclovir is effective for prevention of herpes zoster in myeloma patients treated with bortezomib: a report from the Korean Multiple Myeloma Working Party (KMMWP) Retrospective Study. Jpn J Clin Oncol 41:353–357

    Article  Google Scholar 

  25. Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV (2006) International uniform response criteria for multiple myeloma. Leukemia 20:1467–1473

    Article  CAS  Google Scholar 

  26. Laubach JP, Mahindra A, Mitsiades CS, Schlossman RL, Munshi NC, Ghobrial IM, Carreau N, Hideshima T, Anderson KC, Richardson PG (2009) The use of novel agents in the treatment of relapsed and refractory multiple myeloma. Leukemia 23:2222–2232

    Article  CAS  Google Scholar 

  27. Ben-Efraim S (2001) Immunomodulating anticancer alkylating drugs: targets and mechanisms of activity. Curr Drug Targets 2:197–212

    Article  CAS  Google Scholar 

  28. Matar P, Rozados VR, Gervasoni SI, Scharovsky GO (2002) Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model. Cancer Immunol Immunother 50:588–596

    Article  CAS  Google Scholar 

  29. Bang SM, Lee JH, Yoon SS, Park S, Min CK, Kim CC, Suh C, Sohn SK, Min YH, Lee JJ, Kim K, Seong CM, Yoon HJ, Cho KS, Jo DY, Lee KH, Lee NR, Kim CS (2006) A multicenter retrospective analysis of adverse events in Korean patients using bortezomib for multiple myeloma. Int J Hematol 83:309–313

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. Kaufman JL, Nooka A, Vrana M, Gleason C, Heffner LT, Lonial S (2010) Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma: a retrospective study. Cancer 116:3143–3151

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea

    Jae-Sook Ahn, Deok-Hwan Yang, Sung-Hoon Jung, Hyung Chul Park, Soo-Young Bae, Yeo-Kyeoung Kim, Hyeoung-Joon Kim & Je-Jung Lee

  2. Department of Hematology, Kyungpook National University Hospital, Daegu, Republic of Korea

    Joon Ho Moon & Sang Kyun Sohn

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Correspondence to Je-Jung Lee.

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Ahn, JS., Yang, DH., Jung, SH. et al. A comparison of bortezomib, cyclophosphamide, and dexamethasone (Vel-CD) chemotherapy without and with thalidomide (Vel-CTD) for the treatment of relapsed or refractory multiple myeloma. Ann Hematol 91, 1023–1030 (2012). https://doi.org/10.1007/s00277-012-1420-7

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