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Bortezomib-containing regimens (BCR) for the treatment of non-transplant eligible multiple myeloma

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Abstract

In multiple myeloma (MM) patients ineligible for transplant, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor with anti-myeloma effects, have been reported. We aimed to evaluate the impact of different bortezomib-containing regimens (BCR) for the treatment of transplant-ineligible MM. All- consecutive patients treated with BCR at our institution from 01/05 to 02/16 were evaluated. With a median of 6 cycles, an overall response rate of 95.2, 80.9, and 76.3% was observed for patients treated with cyclophosphamide-bortezomib-dexamethasone (CyBorD), bortezomib-melphalan-prednisone (VMP), and bortezomib-dexamethasone (VD), respectively (p = 0.03). The median overall survival was similar between the three different BCR, but a trend for better progression-free survival was noted in favor of CyBorD. BCR are efficacious in the treatment of transplant-ineligible MM. Patients receiving continuous therapy (CT) exhibited better outcomes, suggesting that strategies to prevent toxicity and increase the cumulative dose are warranted.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Boccadoro M, Morgan G, Cavenagh J (2005) Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int 5:18

    Article  PubMed  PubMed Central  Google Scholar 

  3. Reddy N, Czuczman MS (2010) Enhancing activity and overcoming chemoresistance in hematologic malignancies with bortezomib: preclinical mechanistic studies. Ann Oncol 21:1756–1764

    Article  CAS  PubMed  Google Scholar 

  4. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS et al (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359:906–917

    Article  CAS  PubMed  Google Scholar 

  5. Mateos MV, Bringhen S, Richardson PG, Lahuerta JJ, Larocca A, Oriol A, Boccadoro M, Garcia-Sanz R, Di Raimondo F, Esseltine DL et al (2014) Bortezomib cumulative dose, efficacy, and tolerability with three different bortezomib-melphalan-prednisone regimens in previously untreated myeloma patients ineligible for high-dose therapy. Haematologica 99:1114–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mateos MV (2011) Subcutaneous bortezomib: a step towards optimised drug use. Lancet Oncol 12:410–411

    Article  PubMed  Google Scholar 

  7. Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V, Cangialosi C, Caravita T, Morabito F, Musto P et al (2007) Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood 109:2767–2772

    CAS  PubMed  Google Scholar 

  8. Palumbo A, Gay F, Cavallo F, Di Raimondo F, Larocca A, Hardan I, Nagler A, Petrucci MT, Hajek R, Pezzatti S et al (2015) Continuous therapy versus fixed duration of therapy in patients with newly diagnosed multiple myeloma. J Clin Oncol 33:3459–3466

    Article  CAS  PubMed  Google Scholar 

  9. Palumbo A, Mateos MV, Bringhen S, San Miguel JF (2011) Practical management of adverse events in multiple myeloma: can therapy be attenuated in older patients? Blood Rev 25:181–191

    Article  CAS  PubMed  Google Scholar 

  10. Yagi H, Fujiwara R, Sano K, Yamazaki K, Hanamoto H, Tsubaki K (2013) Reduced-dosage of three drugs combination of cyclophosphamide, bortezomib and dexamethasone (reduced-CyBorD) is suitable for elderly frail patients with multiple myeloma. Blood 122:1963

  11. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG et al (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  PubMed  PubMed Central  Google Scholar 

  12. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Laumann K, Hentz J, Pirooz NA, Piza JG, Tiedemann R et al (2010) Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood 115:3416–3417

    Article  CAS  PubMed  Google Scholar 

  13. Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R et al (2015) Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens. J Clin Oncol 33:3921–3929

    Article  CAS  PubMed  Google Scholar 

  14. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D (1998) 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. European Group for Blood and Marrow Transplant Br J Haematol 102:1115–1123

    CAS  Google Scholar 

  15. Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P et al (2006) International uniform response criteria for multiple myeloma. Leukemia 20:1467–1473

    Article  CAS  PubMed  Google Scholar 

  16. Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, Blade J, Richardson P, Orlowski R, Siegel D et al (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  PubMed  PubMed Central  Google Scholar 

  17. Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ (1999) Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 59:2615–2622

    CAS  PubMed  Google Scholar 

  18. Reeder CB, Reece DE, Kukreti V, Mikhael JR, Chen C, Trudel S, Laumann K, Vohra H, Fonseca R, Bergsagel PL et al (2014) Long-term survival with cyclophosphamide, bortezomib and dexamethasone induction therapy in patients with newly diagnosed multiple myeloma. Br J Haematol 167:563–565

    Article  CAS  PubMed  Google Scholar 

  19. Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL et al (2010) Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 116:679–686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R et al (2008) Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 112:3107–3114

    Article  CAS  PubMed  Google Scholar 

  21. Areethamsirikul N, Masih-Khan E, Chu CM, Jimenez-Zepeda V, Reece DE, Trudel S, Kukreti V, Tiedemann R, Chen C (2015) CyBorD induction therapy in clinical practice. Bone Marrow Transplant 50:375–379

    Article  CAS  PubMed  Google Scholar 

  22. Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K et al (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366:1759–1769

    Article  CAS  PubMed  Google Scholar 

  23. Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N et al (2014) Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371:906–917

    Article  CAS  PubMed  Google Scholar 

  24. Durie B, Hoering A, Rajkumar SV, Abidi M, Epstein J, Kahanic S, Thakuri M, Reu F, Reynolds C, Sexton R, Orlowski R, Barlogie B, Dispenzieri A (2015) Bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT): results of the randomized phase III trial SWOG S0777. Blood 126:25

  25. Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S et al (2016) Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood 127:1102–1108

    Article  CAS  PubMed  Google Scholar 

  26. Palumbo A, Mina R (2013) Part II: role of maintenance therapy in transplant-ineligible patients. J Natl Compr Cancer Netw 11:43–49

    CAS  Google Scholar 

  27. Palumbo A, Niesvizky R (2012) Sustained disease control in transplant-ineligible patients: the role of continuous therapy. Leuk Res 36(Suppl 1):S19–S26

    Article  PubMed  Google Scholar 

  28. Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T et al (2010) 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 28:5101–5109

    Article  CAS  PubMed  Google Scholar 

  29. Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID et al (2014) Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol 32:634–640

    Article  CAS  PubMed  Google Scholar 

  30. Mateos MV (2012) How to maintain patients on long-term therapy: understanding the profile and kinetics of adverse events. Leuk Res 36(Suppl 1):S35–S43

    Article  PubMed  Google Scholar 

  31. Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, de Paz R, Garcia-Larana J, Bengoechea E, Martin A, Mediavilla JD et al (2010) 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 11:934–941

    Article  CAS  PubMed  Google Scholar 

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Contribution

VJZ and NB performed research; collected, analyzed, and interpreted data; performed statistical analysis; and wrote the manuscript; and PN, JT, and PD designed research, analyzed and interpreted data, and wrote the manuscript.

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Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Tom Baker Cancer Center, 1331 29th St, NW, Calgary, AB, T2N 4N2, Canada

    Victor H Jimenez-Zepeda, Peter Duggan, Paola Neri, Jason Tay & Nizar J Bahlis

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  1. Victor H Jimenez-Zepeda
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  2. Peter Duggan
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  3. Paola Neri
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  4. Jason Tay
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  5. Nizar J Bahlis
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Correspondence to Victor H Jimenez-Zepeda.

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Approval for the review of these records was obtained from the TBCC Institutional Review Board and was in accordance with the Declaration of Helsinki.

Conflict of interest disclosures

VJZ, NB, PN, PD, and JT have received honoraria from Janssen. VJZ have received honoraria from Amgen and Celgene.

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Jimenez-Zepeda, V.H., Duggan, P., Neri, P. et al. Bortezomib-containing regimens (BCR) for the treatment of non-transplant eligible multiple myeloma. Ann Hematol 96, 431–439 (2017). https://doi.org/10.1007/s00277-016-2901-x

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  • DOI: https://doi.org/10.1007/s00277-016-2901-x

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