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Real world outcomes of lenalidomide or bortezomib maintenance in patients with multiple myeloma not undergoing stem cell transplantation

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Abstract

Maintenance is one form of long-term therapies in multiple myeloma (MM). Lenalidomide and bortezomib are two commonly used options. The role of maintenance in patients not undergoing transplant remains unclear. A total of 248 newly diagnosed MM patients who received over 180 days of any standard-of-care induction therapy and did not receive autologous stem cell transplantation were included. Patients either receive lenalidomide, bortezomib or no maintenance. Patterns of usage, survival benefit, discontinuation status were analyzed. 93, 99 and 56 patients received no, lenalidomide (Len) and bortezomib (Bor) maintenance respectively. Patients receiving Bor had a higher incidence of traditional high-risk cytogenetics (14.0% (No) vs 14.1% (Len) vs 41.1% (Bor), P < 0.001). Len maintenance conferred a superior progression-free survival (PFS) and overall survival (OS) compared to no maintenance (median PFS, 60.1 vs 26.9 months, P = 0.003; median OS, NR vs 56.7 months, P = 0.046), with a near independent impact on PFS (adjusted HR 0.580, P = 0.058). The PFS and OS benefit of Len maintenance was seen in subgroups of ISS stage I/II, traditional standard-risk cytogenetics, and pre-maintenance < CR. Bor maintenance did not confer PFS or OS benefit for the entire cohort, but improved OS in patients with pre-maintenance < CR. Discontinuation due to toxicity was recorded in 11.1% and 8.9% of patients receiving Len or Bor maintenance respectively. Our study supports lenalidomide maintenance as the standard-of-care in MM patients not undergoing transplant. Further studies are warranted for bortezomib maintenance in the non-transplant setting, and better maintenance strategy is needed for patients with adverse prognostic factors.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Palumbo A, Gay F, Cavallo F et al (2015) Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma. J Clin Oncol 33(30):3459–3466

    Article  CAS  PubMed  Google Scholar 

  2. Ludwig H, Zojer N (2017) Fixed duration vs continuous therapy in multiple myeloma. Hematology Am Soc Hematol Educ Program 2017(1):212–222

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gay F, Jackson G, Rosiñol L et al (2018) Maintenance Treatment and Survival in Patients With Myeloma: A Systematic Review and Network Meta-analysis. JAMA Oncol 4(10):1389–1397

    Article  PubMed  PubMed Central  Google Scholar 

  4. Attal M, Lauwers-Cances V, Marit G et al (2012) Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366(19):1782–1791

    Article  CAS  PubMed  Google Scholar 

  5. McCarthy PL, Owzar K, Hofmeister CC et al (2012) Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 366(19):1770–1781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Palumbo A, Cavallo F, Gay F et al (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371(10):895–905

    Article  PubMed  Google Scholar 

  7. Jackson GH, Davies FE, Pawlyn C et al (2019) Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 20(1):57–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sonneveld P, Schmidt-Wolf IG, van der Holt B et al (2012) Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol 30(24):2946–2955

    Article  CAS  PubMed  Google Scholar 

  9. Dimopoulos MA, Gay F, Schjesvold F et al (2019) Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 393(10168):253–264

    Article  CAS  PubMed  Google Scholar 

  10. McCarthy PL, Holstein SA, Petrucci MT et al (2017) Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol 35(29):3279–3289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chakraborty R, Muchtar E, Kumar SK et al (2018) Outcomes of maintenance therapy with lenalidomide or bortezomib in multiple myeloma in the setting of early autologous stem cell transplantation. Leukemia 32(3):712–718

    Article  CAS  PubMed  Google Scholar 

  12. Huang J, Phillips S, Byrne M et al (2018) Lenalidomide vs bortezomib maintenance choice post-autologous hematopoietic cell transplantation for multiple myeloma. Bone Marrow Transplant 53(6):701–707

    Article  CAS  PubMed  Google Scholar 

  13. Palumbo A, Hajek R, Delforge M et al (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366(19):1759–1769

    Article  CAS  PubMed  Google Scholar 

  14. Palumbo A, Bringhen S, Larocca A 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(7):634–640

    Article  CAS  PubMed  Google Scholar 

  15. Dimopoulos MA, Špička I, Quach H et al (2020) Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial. J Clin Oncol 38(34):4030–4041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Balitsky AK, Karkar A, McCurdy A, Rochwerg B, Mian HS (2020) Maintenance therapy in transplant ineligible adults with newly-diagnosed multiple myeloma: A systematic review and meta-analysis. Eur J Haematol 105(5):626–634

    Article  PubMed  Google Scholar 

  17. Callander NS, Baljevic M, Adekola K et al (2022) NCCN Guidelines® Insights: Multiple Myeloma, Version 3.2022. J Natl Compr Canc Netw. 20(1):8–19

    Article  PubMed  Google Scholar 

  18. Dimopoulos MA, Moreau P, Terpos E et al (2021) Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 32(3):309–322

    Article  CAS  PubMed  Google Scholar 

  19. Shen M, Zhang J, Tang R et al (2021) Ixazomib-based maintenance therapy after bortezomib-based induction in patients with multiple myeloma not undergoing transplantation: A real-world study. Cancer Med. https://doi.org/10.1002/cam4.4313

    Article  PubMed  PubMed Central  Google Scholar 

  20. Noguchi Y, Iriyama N, Takahashi H et al (2021) Maintenance Therapy With Bortezomib and Dexamethasone for Transplant-ineligible Patients With Multiple Myeloma. Cancer Diagn Progn 1(2):35–42

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rajkumar SV, Dimopoulos MA, Palumbo A et al (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15(12):e538–e548

    Article  PubMed  Google Scholar 

  22. Kumar S, Paiva B, Anderson KC et al (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17(8):e328–e346

    Article  PubMed  Google Scholar 

  23. Benboubker L, Dimopoulos MA, Dispenzieri A et al (2014) Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371(10):906–917

    Article  CAS  PubMed  Google Scholar 

  24. Rosiñol L, Oriol A, Teruel AI et al (2017) Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia 31(9):1922–1927

  25. Avet-Loiseau H, Leleu X, Roussel M et al (2010) Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol 28(30):4630–4634

    Article  CAS  PubMed  Google Scholar 

  26. Morgan GJ, Davies FE, Gregory WM et al (2013) Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res 19(21):6030–6038

    Article  CAS  PubMed  Google Scholar 

  27. Sonneveld P, Avet-Loiseau H, Lonial S et al (2016) Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood 127(24):2955–2962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nooka AK, Kaufman JL, Muppidi S et al (2014) Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia 28(3):690–693

    Article  CAS  PubMed  Google Scholar 

  29. Rajkumar SV (2022) Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol 97(8):1086–1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Moreau P, Hulin C, Perrot A et al (2021) Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol 22(10):1378–1390

    Article  CAS  PubMed  Google Scholar 

  31. Voorhees PM, Kaufman JL, Laubach J et al (2020) Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood 136(8):936–945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ihorst G, Waldschmidt J, Schumacher M, Wäsch R, Engelhardt M (2015) Analysis of survival by tumor response: have we learnt any better? Ann Hematol 94(9):1615–1616

    Article  PubMed  Google Scholar 

  33. Lu J, Lu J, Chen W et al (2014) Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. Blood Cancer J 4(8):e239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by Natural Science Foundation of Shanghai (Grant No. 22ZR1411400).

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Authors and Affiliations

  1. Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China

    Tianhong Xu, Yang Yang, Jing Li, Jiadai Xu, Wenjing Wang, Yawen Wang, Aziguli Maihemaiti, Liang Ren, Tianwei Lan, Chi Zhou, Panpan Li, Pu Wang & Peng Liu

  2. Department of Hematology, Shanghai Geriatric Medical Center, Shanghai, China

    Tianhong Xu & Peng Liu

Authors
  1. Tianhong Xu
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  2. Yang Yang
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  3. Jing Li
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Contributions

Peng Liu and Tianhong Xu designed and conceived the study. Tianhong Xu analyzed, interpreted the data and drafted the manuscript. Tianhong Xu, Yang Yang, Jing Li, Jiadai Xu, Wenjing Wang, Yawen Wang, Aziguli Maihemaiti, Liang Ren, Tianwei Lan, Chi Zhou, Panpan Li and Pu Wang collected and reviewed the data. Peng Liu approved the final draft of the paper.

Corresponding author

Correspondence to Peng Liu.

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Ethics approval

This study was approved by the ethics committee of Zhongshan Hospital (B2017-031R). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

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Informed consent was obtained from all patients for being included in the study.

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The authors have no conflicts of interest to disclose.

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Xu, T., Yang, Y., Li, J. et al. Real world outcomes of lenalidomide or bortezomib maintenance in patients with multiple myeloma not undergoing stem cell transplantation. Ann Hematol 102, 1171–1184 (2023). https://doi.org/10.1007/s00277-023-05148-y

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