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Bortezomib plus dexamethasone for relapsed or treatment refractory multiple myeloma: the collaborative study at six institutes in Kyoto and Osaka

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Abstract

We conducted a retrospective collaborative investigation of bortezomib (Bor) plus dexamethasone (Dex) therapy (BD Tx) for 88 relapsed or refractory (Rel/Ref) MM patients at six institutes. One cycle BD Tx comprised of Bor (1.3 mg/m2/day) on days 1, 4, 8 and 11, and Dex on days 1, 2, 4, 5, 8, 9, 11 and 12, every 21 days, and the mean number of BD Tx cycles was 3. The overall response rate was 66.9%, the median overall survival (OS) was 510 days, and the median progression-free survival (PFS) was 113 days. Attainment of partial response (PR) with the first course of BD Tx associated with the longer OS and PFS and late good responder, while no patient who did not achieve PR with the first cycle attained better than very good PR (VGPR) with the subsequent BD Tx. Patient age of less than 64 years old also associated with the longer OS and PFS. In addition, both an earlier disease stage and Dex dosage had a significant impact on OS, while the attainment of VGPR within 2 cycles had a significantly longer PFS. Earlier BD Tx courses may be predictive for the subsequent therapeutic pathway of Rel/Ref MM.

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References

  1. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.

    Article  CAS  PubMed  Google Scholar 

  2. Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111:2962–72.

    Article  CAS  PubMed  Google Scholar 

  3. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–98.

    Article  CAS  PubMed  Google Scholar 

  4. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, 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.

    Article  CAS  PubMed  Google Scholar 

  5. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. Extended follow-up of phase II trial in relapsed, refractory multiple myeloma. Final time-to-event results from the SUMMIT trial. Cancer. 2006;106:1316–9.

    Article  CAS  PubMed  Google Scholar 

  6. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma. Br J Haematol. 2007;137:429–35.

    Article  CAS  PubMed  Google Scholar 

  7. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapse, refractory myeloma. N Engl J Med. 2003;348:2609–17.

    Article  CAS  PubMed  Google Scholar 

  8. Jagannath S, Durie BG, Wolf JL, Camacho ES, Irwin D, Lutzky J, et al. Extended follow-up of a phase 2 trial of bortezomib alone and in combination with dexamethasone for the frontline treatment of multiple myeloma. Br J Haematol. 2009;146:619–26.

    Article  CAS  PubMed  Google Scholar 

  9. Jagannath S, Barlogie B, Berenson JR, Siegel DS, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Esseltine DL, Anderson KC. Updated survival analyses after prolonged follow-up of the phase 2, multicenter CREST study of bortezomib in relapsed or refractory multiple myeloma. Br J Haematol. 2008;143:537–40.

    PubMed  Google Scholar 

  10. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma. Blood. 2005;106:2977–81.

    Article  CAS  PubMed  Google Scholar 

  11. Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A, et al. Randomised 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.

    Article  CAS  PubMed  Google Scholar 

  12. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood. 2008;112:1593–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73.

    Article  CAS  PubMed  Google Scholar 

  15. Gotoh A, Ohyashiki K, Oshimi K, Usui N, Hotta T, Dan K, et al. Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan; a questionnaire-based report from the “lung injury by bortezomib” joint committee of the Japanese society of haematology and the Japanese society of clinical haematology. Int J Hematol. 2006;84:406–12.

    Article  CAS  PubMed  Google Scholar 

  16. Miyakoshi S, Kami M, Yuji K, Matsumura T, Takatoku M, Sasaki M, et al. Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma. Blood. 2006;107:3492–4.

    Article  CAS  PubMed  Google Scholar 

  17. Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, 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.

    Article  CAS  PubMed  Google Scholar 

  18. Vogl DT, Stadtmauer EA, Richardson PG, Sonneveld P, Schuster MW, Irwin D, et al. Impact of prior therapies on the relative efficacy of bortezomib compared with dexamethasone in patients with relapsed/refractory multiple myeloma. Br J Haematol. 2009;147:531–4.

    Article  CAS  PubMed  Google Scholar 

  19. 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;354:1021–30.

    Article  CAS  PubMed  Google Scholar 

  20. Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, et al. A phase 2 study or two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004;127:165–72.

    Article  CAS  PubMed  Google Scholar 

  21. Ohguchi H, Sugawara T, Ishikawa I, Okuda M, Tomiya Y, Yamamoto J, et al. A retrospective analysis of bortezomib therapy for Japanese patients with relapsed or refractory multiple myeloma: beta2-microglobulin associated with time to progression. Int J Hematol. 2009;89:342–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We wish to thank Drs K Taniguchi, Y Tsutsumi, M Yamamoto, N Sasaki, M Ohshiro, Y Shimura, S Mizutani and R Nakayama for their scientific support. This work was partly supported by the Award in Aki’s Memory from the International Myeloma Foundation (to J.K.).

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan

    Tsutomu Kobayashi, Junya Kuroda, Kazuho Shimura, Miki Kiyota, Hitoji Uchiyama, Yosuke Matsumoto, Shigeo Horiike & Masafumi Taniwaki

  2. Department of Hematology, Aiseikai Yamashina Hospital, Kyoto, Japan

    Kazuho Shimura & Hiroto Kaneko

  3. Department of Hematology, Kyoto Second Red Cross Hospital, Kyoto, Japan

    Teruaki Akaogi, Eri Kawata, Miki Kiyota, Takashi Tanaka & Yutaka Kobayashi

  4. Department of Hematology, Matsushita Memorial Hospital, Osaka, Japan

    Yuri Kamitsuji & Nobuhiko Uoshima

  5. Department of Hematology, Kyoto Social Insurance Hospital, Kyoto, Japan

    Satoshi Murakami, Mayumi Hatsuse, Akira Okano & Chihiro Shimazaki

  6. Department of Hematology, Kyoto First Red Cross Hospital, Kyoto, Japan

    Toshiki Iwai, Satomi Ueda, Masahiko Koshida & Yutaka Ueda

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  1. Tsutomu Kobayashi
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  2. Junya Kuroda
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  19. Yutaka Ueda
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  20. Yutaka Kobayashi
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Corresponding author

Correspondence to Junya Kuroda.

Electronic supplementary material

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12185_2010_696_MOESM1_ESM.tif

Impact of the number of regimen prior to BD on OS and PFS for BD Tx. Kaplan-Meier plots of OS (a) and PFS (b) according to the number of prior regimens 1-2 (solid line), 3-5 (dotted line) and 6 or more (gray line) regimens (TIFF 98 kb)

Supplementary material 2 (TIFF 122 kb)

Supplementary material 3 (TIFF 108 kb)

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Kobayashi, T., Kuroda, J., Shimura, K. et al. Bortezomib plus dexamethasone for relapsed or treatment refractory multiple myeloma: the collaborative study at six institutes in Kyoto and Osaka. Int J Hematol 92, 579–586 (2010). https://doi.org/10.1007/s12185-010-0696-4

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  • DOI: https://doi.org/10.1007/s12185-010-0696-4

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