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Sequential vincristine, adriamycin, dexamethasone (VAD) followed by bortezomib, thalidomide, dexamethasone (VTD) as induction, followed by high-dose therapy with autologous stem cell transplant and consolidation therapy with bortezomib for newly diagnosed multiple myeloma: results of a phase II trial

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Abstract

Incorporation of novel agents has resulted in an improved response rate and reduced side effects in multiple myeloma. This has prompted combining novel agents in induction chemotherapy in patients with newly diagnosed multiple myeloma. Our patients received 2 cycles of vincristine, adriamycin, dexamethasone (VAD) and then 2 cycles of bortezomib, thalidomide, dexamethasone (VTD) chemotherapy as an induction treatment. Subsequently, autologous stem cell transplantation was performed, and bortezomib was administered as a consolidation therapy. Seventy-one patients were enrolled, and 65 were evaluable for response. After 2 cycles of VAD, the overall response rate was 69%. After VTD, the response rate improved to 97% with a complete response (CR) and near CR rate of 27%. Importantly, patients with cytogenetics, having poor prognostic features, all responded after VTD. Autologous stem cells were successfully collected in all 58 patients with a median CD34+ cell count of 7.12 × 106/kg (range, 1.94–44.7 × 106/kg), except in 1 patient (2%). After ASCT, 36 patients completed bortezomib maintenance with a combined CR and near CR rate approaching 75%. Median time to response was rapid (1.6 months). With a median follow-up duration of 52.7 months, the median TTP was 29.4 months and median OS was not reached. Toxicities proved manageable. In conclusion, sequential VAD and VTD induction therapy in patients with newly diagnosed multiple myeloma was active with manageable toxicity and excellent stem cell yields. The incorporation of bortezomib as a consolidation therapy improved the clinical outcome with the expense of rather frequent development of peripheral neuropathy.

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Acknowledgments

The authors would like to thank Sun Jong Lee for her efforts in data collection, Yun Jeong Kim for her administrative assistance, and KMMWP. This work was supported by a grant of (1) the Korea Health 21 R&D Project, Ministry for Health, Welfare and Family Affairs, R.O.K. (A084783) and (2) the Korea Health 21 R&D project, Ministry for Health, Welfare and Family Affairs, R.O.K. (A030001) and in part, by Janssen Korea.

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Authors and Affiliations

  1. The Armed Forces Capital Hospital, Seoul, South Korea

    Hye Jin Kim

  2. Clinical Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Sung-Soo Yoon & Dong Soon Lee

  3. Kyungbook National University Hospital, Daegu, South Korea

    Sang Kyun Sohn

  4. National Cancer Center, Goyang, Kyunggi, South Korea

    Hyeon Seok Eom

  5. Daegu Fatima Hospital, Daegu, South Korea

    Jung Lim Lee

  6. Pusan University Hospital, Pusan, South Korea

    Joo Seup Chung

  7. SungKyungKwan University, Samsung Medical Center, Seoul, South Korea

    Kihyun Kim

  8. Asan Medical Center, Seoul, South Korea

    Cheolwon Suh

  9. Soon Chun Hyang University Hospital, Seoul, South Korea

    Jong Ho Won

  10. Yonsei University Severance Hospital, Seoul, South Korea

    Jin Seok Kim

  11. Ajou University Hospital, Suwon, Kyunggi, South Korea

    Joon Seong Park

  12. Korea Institute of Radiological and Medical Science, Seoul, South Korea

    Hye Jin Kang

  13. Ewha Women’s University Hospital, Seoul, South Korea

    Chu Myong Seong

  14. Inha University Hospital, Incheon, South Korea

    Cheol Soo Kim

  15. Chung-Ang University Hospital, Seoul, South Korea

    Sang Jae Lee

  16. Gachon University Gil Hospital, Incheon, South Korea

    Jae Hoon Lee

  17. Division of Hematology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehang-ro, Jongno-gu, Seoul, 110-744, South Korea

    Sung-Soo Yoon

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  1. Hye Jin Kim
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Correspondence to Sung-Soo Yoon.

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Kim, H.J., Yoon, SS., Lee, D.S. et al. Sequential vincristine, adriamycin, dexamethasone (VAD) followed by bortezomib, thalidomide, dexamethasone (VTD) as induction, followed by high-dose therapy with autologous stem cell transplant and consolidation therapy with bortezomib for newly diagnosed multiple myeloma: results of a phase II trial. Ann Hematol 91, 249–256 (2012). https://doi.org/10.1007/s00277-011-1298-9

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