Skip to main content
Log in

Management and outcome of 500 multiple myeloma patients treated for first relapse outside clinical studies

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

Abstract

Treatment options for multiple myeloma (MM) at 1st relapse are expanding. The current study compared common 2nd line regimens administered in a real-world setting. MM patients registered in Maccabi health care services and treated with second line therapy during 2014–2020 were evaluated, analyzing factors affecting time to third line therapy (TT3T). The study included 500 MM patients, previously treated with proteasome inhibitor (PI)–based induction. Median age at second line treatment was 68.5 years (IQR: 61.6–76.4). Most patients received a triplet based induction composed of PI (n = 471, 94.2%), with (n = 71) or without IMID (n = 400), followed by second line treatment composed of lenalidomide-dexamethasone (RD) (n = 225, 45%) or lenalidomide–dexamethasone–daratumumab (RD-Dara (n = 104, 20.8%)). Multivariable analysis confirmed treatment type (RD-Dara vs. IMID) to be associated with a lower risk to progress to third line therapy; (HR = 0.5, 95% CI 0.3–0.86, p = 0.012). Within a median follow-up period of 22.5 months (intraquartile range 11.1–39.4 m), median TT3T was not reached in patients receiving RD-Dara vs. 32.4 months (95% CI 18.0–46.8 m) with IMID, 18 months (95% CI 10.4–25.6 m) with IMID-PI and 12.1 months (95% CI 5.6–18.7 m) with PI-based regimen. In contrast, PI vs. IMID-based therapy and increased body weight were associated with a higher likelihood of progression (HR = 2.56 (95% CI 1.49–4.42); HR = 1.43, (95% CI 0.96–2.14), p = 0.08). To conclude, second line therapy with RD-Dara was associated with a significantly longer TT3T compared with IMID-based regimen, longer than obtained with PI-IMID and PI-based regimens, in patients treated outside clinical studies and previously exposed to bortezomib.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Rosiñol L, Oriol A, Teruel AI et al (2012) Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 120(8):1589–1596 [Cited 2023 Aug 29]

    Article  PubMed  Google Scholar 

  2. San Miguel JF, Schlag R, Khuageva NK, et al (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359(9):906–17 [cited 2022 Jun 19]. Available from: www.nejm.org. Accessed 29 Aug 2023

  3. Bahlis NJ, Dimopoulos MA, White DJ, et al (2020) Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia 34(7):1875–84 [cited 2022 Jan 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/32001798/. Accessed 29 Aug 2023

  4. Stewart AK, Rajkumar SV, Dimopoulos MA, et al (2015) Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 372(2):142–52 [cited 2022 Jan 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/25482145/. Accessed 29 Aug 2023

  5. Moreau P, Masszi T, Grzasko N, et al (2016) Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 374(17):1621–34 [cited 2022 Jan 18]. Available from: https://www.nejm.org/doi/10.1056/NEJMoa1516282. Accessed 29 Aug 2023

  6. Dimopoulos MA, Moreau P, Palumbo A, et al (2016 ) Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol 17(1):27–38 [cited 2022 Jan 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/26671818/. Accessed 29 Aug 2023

  7. Dimopoulos MA, Swern AS, Li JS, et al (2014) Efficacy and safety of long-term treatment with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. Blood Cancer J 4(11):e257–e257 [cited 2022 Jan 18]. Available from: https://www.nature.com/articles/bcj201477. Accessed 29 Aug 2023

  8. Richardson PG, San Miguel JF, Moreau P, et al (2018) Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting. Blood Cancer J  8(11) [cited 2022 Jan 19]. Available from: https://pubmed.ncbi.nlm.nih.gov/30413684/. Accessed 29 Aug 2023

  9. Chari A, Richardson PG, Romanus D, et al (2020) Real-world outcomes and factors impacting treatment choice in relapsed and/or refractory multiple myeloma (RRMM): a comparison of VRd, KRd, and IRd. Expert Rev Hematol 13(4):421–33 [cited 2022 Jan 19]. Available from: https://pubmed.ncbi.nlm.nih.gov/32148109/. Accessed 29 Aug 2023

  10. Chari A, Romanus D, Palumbo A, et al (2020) Randomized clinical trial representativeness and outcomes in real-world patients: comparison of 6 hallmark randomized clinical trials of relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk 20(1):8–17.e16 [cited 2022 Jan 19]. Available from: https://pubmed.ncbi.nlm.nih.gov/31722839/. Accessed 29 Aug 2023

  11. 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):e538–48 [cited 2021 Mar 24]. Available from: https://pubmed.ncbi.nlm.nih.gov/25439696/ Accessed 29 Aug 2023

  12. Hari PN, Zhang MJ, Roy V et al (2009) Is the international staging system superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous transplant. Leukemia 23(8):1528–1534 [Cited 2023 Aug 29]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rajkumar SV, Richardson P, San Miguel JF (2015) Guidelines for determination of the number of prior lines of therapy in multiple myeloma. Blood  126(7):921–2[cited 2023 Mar 16]. Available from: https://pubmed.ncbi.nlm.nih.gov/26272048/. Accessed 29 Aug 2023

  14. Weitzman D, Chodick G, Shalev V, Grossman C, Grossman E (2014) Prevalence and factors associated with resistant hypertension in a large health maintenance organization in Israel. Hypertens (Dallas, Tex 1979)  64(3):501–7 [cited 2022 Jan 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/24958503/. Accessed 29 Aug 2023

  15. Shalev V, Chodick G, Goren I, Silber H, Kokia E, Heymann AD (2011) The use of an automated patient registry to manage and monitor cardiovascular conditions and related outcomes in a large health organization. Int J Cardiol 152(3):345–9 [cited 2022 Jan 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/20826019/. Accessed 29 Aug 2023

  16. Chodick G, Heymann AD, Shalev V, Kookia E (2003) The epidemiology of diabetes in a large Israeli HMO. Eur J Epidemiol 18(12):1143–6 [cited 2022 Jan 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/14758871/. Accessed 29 Aug 2023

  17. Dimopoulos MA, Oriol A, Nahi H, et al (2016) Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med  375(14):1319–31 [cited 2022 Jan 19]. Available from: https://pubmed.ncbi.nlm.nih.gov/27705267/. Accessed 29 Aug 2023

  18. Durie BGM, Salmon SE (1975) A clinical staging system for multiple myeloma correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 36(3):842–854 [Cited 2023 Aug 29]

    Article  CAS  PubMed  Google Scholar 

  19. Palumbo A, Avet-Loiseau H, Oliva S et al (2015) Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol 33(26):2863–2869 [Cited 2023 Aug 29]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Weil C, Gelerstein S, Sharman Moser S et al (2019) Real-world epidemiology, treatment patterns and survival of multiple myeloma patients in a large nationwide health plan. Leuk Res. 85:106219 [Cited 2023 Aug 29]. https://doi.org/10.1016/j.leukres.2019.106219

    Article  PubMed  Google Scholar 

  21. Voorhees PM, Kaufman JL, Laubach JP, et al (2020) Daratumumab, lenalidomide, bortezomib, & dexamethasone for transplant-eligible newly diagnosed multiple myeloma: GRIFFIN. Blood  [cited 2020 Jun 28]. Available from: https://pubmed.ncbi.nlm.nih.gov/32325490/. Accessed 29 Aug 2023

Download references

Funding

AbbVie funded the research for this study. No honoraria or payments were made for authorship.

Author information

Authors and Affiliations

Authors

Contributions

All authors designed the protocol and the study concept. Naama Yekutiel extracted and analyzed the data. Irit Avivi, Naama Yekutiel, Gabriel Chodick, Neta Frankel, and Tamir Shragai interpreted the results. Irit Avivi, Naama Yekutiel, and Gabriel Chodick wrote the first draft of the manuscript. All authors provided feedback on the manuscript, writing, reviewing, and approving the final version for submission.

Corresponding author

Correspondence to Irit Avivi.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Competing interests

Prof. Gabriel Chodick, Naama Yekutiel, Clara Weil, Prof. Yael C. Cohen, and Dr. Tamir Shragai do not have any conflict of interest. Prof. Irit Avivi was a consultant to abbvie and received research funding. Dr. Moshe Grunspan, Dr. Noa Rivlin, Dr. Neta Frankel, and Dr. Raanan Cohen are employees of AbbVie and own AbbVie stock.

Additional information

Publisher's note

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

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Avivi, I., Yekutiel, N., Shragai, T. et al. Management and outcome of 500 multiple myeloma patients treated for first relapse outside clinical studies. Ann Hematol 102, 3075–3081 (2023). https://doi.org/10.1007/s00277-023-05307-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-023-05307-1

Keywords

Navigation