Skip to main content

Advertisement

SpringerLink
Log in

Efficacy and safety of modified BLd therapy for Japanese patients with transplant-ineligible multiple myeloma

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

The BLd regimen, which is a triplet regimen of bortezomib (Bor), lenalidomide (Len), and dexamethasone (Dex), is effective against newly diagnosed multiple myeloma (NDMM). However, non-hematological toxicities, such as peripheral neuropathy (PN), often hamper long-term continuation of the regimen, particularly in older adult patients. In this study, we examined the efficacy and safety of the modified BLd regimen with reduced-intensity Bor and standard-dose Len. The chemotherapy regimen consisted of 1.3 mg/m2 Bor administered subcutaneously on days 1 and 8, 25 mg Len administered on days 1–14, and 20 mg Dex on days 1–2 and 8–9 of a 3 week cycle for 8 cycles, followed by a 4 week cycle of Dex (40 mg weekly). Among the 30 patients enrolled, 60.0% (95% CI 40.6–77.3) had a very good partial response or better, and the best overall response rate was 96.7% (95% CI 82.8–99.9). Eight patients (26.7%) achieved a complete response. Grade 3 or higher PN was not observed and hematological toxicity was the most common adverse event. The modified BLd regimen showed favorable efficacy with a manageable safety profile, which suggests it could be a treatment option for transplant-ineligible NDMM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Totani H, Ri M, Kato C, Nakashima T, Suzuki N, Hagiwara S, et al. Phase I study of once weekly treatment with bortezomib in combination with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma. Int J Hematol. 2016;103:316–21.

    Article  CAS  Google Scholar 

  2. Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014;123:1461–9.

    Article  CAS  Google Scholar 

  3. Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M, et al. Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia. 2010;24:1769–78.

    Article  CAS  Google Scholar 

  4. Jakubowiak AJ, Griffith KA, Reece DE, Hofmeister CC, Lonial S, Zimmerman TM, et al. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 multiple myeloma research consortium trial. Blood. 2011;118:535–43.

    Article  CAS  Google Scholar 

  5. 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 before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011;118:5752–8.

    Article  CAS  Google Scholar 

  6. 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;116:679–86.

    Article  CAS  Google Scholar 

  7. Roussel M, Facon T, Moreau P, Harousseau JL, Attal M. Firstline treatment and maintenance in newly diagnosed multiple myeloma patients. Recent Results Cancer Res. 2011;183:189–206.

    Article  Google Scholar 

  8. Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119:4375–82.

    Article  CAS  Google Scholar 

  9. Iida S, Ishida T, Murakami H, Ozaki S, Abe M, Hata H, et al. JSH practical guidelines for hematological malignancies, 2018: III. Myeloma-1 multiple myeloma (MM). Int J Hematol. 2019;109:509–38.

    Article  Google Scholar 

  10. Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389:519–27.

    Article  CAS  Google Scholar 

  11. Durie BGM, Hoering A, Sexton R, Abidi MH, Epstein J, Rajkumar SV, et al. Longer term follow-up of the randomized phase III trial SWOG S0777: 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). Blood Cancer J. 2020;10:53.

    Article  Google Scholar 

  12. O’Donnell EK, Laubach JP, Yee AJ, Chen T, Huff CA, Basile FG, et al. A phase 2 study of modified lenalidomide, bortezomib and dexamethasone in transplant-ineligible multiple myeloma. Br J Haematol. 2018;182:222–30.

    Article  Google Scholar 

  13. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–20.

    Article  Google Scholar 

  14. Inagaki A, Tajima E, Uranishi M, Totani H, Asao Y, Ogura H, et al. Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma. Leuk Res. 2013;37:1648–55.

    Article  CAS  Google Scholar 

  15. Suzuki K, Shinagawa A, Uchida T, Taniwaki M, Hirata H, Ishizawa K, et al. Lenalidomide and low-dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: a phase II study. Cancer Sci. 2016;107:653–8.

    Article  CAS  Google Scholar 

  16. Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136:936–45.

    Article  CAS  Google Scholar 

  17. Abdallah N, Kumar SK. Daratumumab in untreated newly diagnosed multiple myeloma. Ther Adv Hematol. 2019;10:2040620719894871.

    Article  CAS  Google Scholar 

  18. Ocio EM, Rodriguez Otero P, Bringhen S, Oliva S, Nogai A, Attal M, et al. Preliminary results from a Phase I study of Isatuximab (ISA) in combination with bortezomib, lenalidomide, dexamethasone (VRd), and in patients with newly diagnosed multiple myeloma (NDMM) non-eligible for transplant. Blood. 2018;132:595.

    Article  Google Scholar 

  19. Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019;393:253–64.

    Article  CAS  Google Scholar 

  20. Alonso R, Cedena MT, Wong S, Shah N, Ríos-Tamayo R, Moraleda JM, et al. Prolonged lenalidomide maintenance therapy improves the depth of response in multiple myeloma. Blood Adv. 2020;4:2163–71.

    Article  CAS  Google Scholar 

  21. Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, et al. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:57–73.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study received financial support from Celgene Co., Ltd. We are grateful to the members of the Data and Safety Monitoring Committee of this study, Hirohiko Shibayama, and Yoichi Imai. We are also grateful for the assistance and cooperation of all members at collaborating institutes and the Japanese Data Center for Hematopoietic Cell Transplantation, especially Ms. Noriko Mizutani and Ms. Shizuka Kobayashi, for their assistance with data management.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan

    Satsuki Murakami, Masaki Ri & Shinsuke Iida

  2. Department of Hematology, Aichi Medical University, Nagakute, Japan

    Satsuki Murakami & Ichiro Hanamura

  3. Department of Hematology, Daido Hospital, Nagoya, Japan

    Masato Ito

  4. Department of Hematology and Infectious Disease, Gifu University Hospital, Gifu, Japan

    Nobuhiko Nakamura & Junichi Kitagawa

  5. Department of Hematology, Gifu Municipal Hospital, Gifu, Japan

    Senji Kasahara & Junichi Kitagawa

  6. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    Yuichiro Inagaki

  7. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Junya Kuroda

  8. Department of Hematology and Rheumatology, Kagoshima University Hospital, Kagoshima, Japan

    Makoto Yoshimitsu

  9. Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan

    Akinao Okamoto

  10. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Miyagi, Japan

    Noriko Fukuhara

  11. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan

    Hirofumi Taji

  12. Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Hiroatsu Iida & Hirokazu Nagai

  13. Division of Hematology Oncology, Chiba Cancer Center, Chiba, Japan

    Hideki Tsujimura

  14. Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

    Miyuki Okura

  15. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Mio Kurata, Yachiyo Kuwatsuka & Yoshiko Atsuta

  16. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan

    Yachiyo Kuwatsuka

  17. Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan

    Yoshiko Atsuta

Authors
  1. Satsuki Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masaki Ri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masato Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nobuhiko Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Senji Kasahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junichi Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuichiro Inagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Junya Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Makoto Yoshimitsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akinao Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Noriko Fukuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hirofumi Taji
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hiroatsu Iida
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hirokazu Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ichiro Hanamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Hideki Tsujimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Miyuki Okura
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Mio Kurata
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yachiyo Kuwatsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Yoshiko Atsuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Shinsuke Iida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaki Ri.

Ethics declarations

Conflict of interest

MR received research funding from Celgene Co., Ltd. JK received declares Honoraria from Janssen Pharmaceutical K.K., and Celgene Co., Ltd. SI received research funding and declared Honoraria from Janssen Pharmaceutical K.K. and Celgene Co., Ltd.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murakami, S., Ri, M., Ito, M. et al. Efficacy and safety of modified BLd therapy for Japanese patients with transplant-ineligible multiple myeloma. Int J Hematol 116, 563–569 (2022). https://doi.org/10.1007/s12185-022-03379-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-022-03379-9

Keywords

Search

Navigation