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Multiple myeloma gammopathies

Improving the identification of frail elderly newly diagnosed multiple myeloma patients

Leukemia volume 35, pages 2715–2719 (2021)Cite this article

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We investigated whether other IMWG-FI score cut-offs would better predict outcome. First, we compared the TD9 rates, PFS and OS between the separate IMWG-FI scores 1–5, instead of using the original dichotomized cut-off for intermediate fit (score 1) and frail (score ≥ 2). Based on the association between the individual scores with TD9 (Table 1a), PFS and OS (Fig. S3), we proposed an alternative cut-off of ≥3 for defining frailty (RFI-1) (Table 1b). This classification was found to be superior in discriminating PFS (Fig. S1b versus Fig. S1a), OS (Fig. 1b versus Fig. 1a), TD9 and TD3 (Table S3) between intermediate fit and frail patients as compared to the original IMWG cut-off of ≥2.

Table 1 Development of revised frailty indexes.
Full size table

Second, we investigated which IMWG-FI parameters (both according to original IMWG-FI cut-offs and as continuous variables) were superior in predicting outcome. Both analyses showed that the CCI best predicted TD9 (Table 1c and Table S4, respectively). Subsequently, we investigated whether another cut-off than CCI ≥ 2 would better predict TD9. A trend for a higher TD9 was found for a CCI of 2, which was statistically significant for CCI ≥ 3 (Table S5). Therefore, in addition to increasing the cut-off for frailty to ≥3 in the RFI-1, we increased the weight of CCI ≥ 3 in the second revised-frailty index (RFI-2) (Table 1b). Again, the RFI-2 was superior in discriminating between the outcome (PFS: Fig. S1c versus S1a; OS: Fig. 1c versus 1a; TD9 and TD3: Table S3) of intermediate fit versus frail patient as compared to the IMWG-FI. Based on AIC model comparison, the difference in OS and PFS between intermediate fit and frail patients was best detected by RFI-1, and in treatment discontinuation by RFI-2 (Table S6).

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Fig. 1: Overall survival between intermediate fit and frail patients according to different frailty indexes.

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Acknowledgements

The authors would like to thank all participating patients and centers and the sponsor of the study by the HOVON data center (special acknowledgements to Heleen Visser-Wisselaar and Henk Hofwegen for their data management support). The authors would like to thank Henk M.W. Verheul for his critical revision of the manuscript. Funding for this study was provided by Janssen Pharmaceutica NV and Koningin Wilhelmina Fonds (KWF).

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Author notes

  1. These authors contributed equally: Claudia A.M. Stege, Kazem Nasserinejad

Authors and Affiliations

  1. Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands

    Claudia A. M. Stege, Inger S. Nijhof, Niels W. C. J. van de Donk, Kaz Groen & Sonja Zweegman

  2. Department of Hematology, HOVON Data Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands

    Kazem Nasserinejad

  3. Department of Internal Medicine, Meander Medical Center, Amersfoort, the Netherlands

    Saskia K. Klein

  4. Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands

    Saskia K. Klein

  5. Department of Internal Medicine, Amstelland Hospital, Amstelveen, the Netherlands

    Gert-Jan Timmers

  6. Department of Hematology, Medical Center Leeuwarden, Leeuwarden, the Netherlands

    Mels Hoogendoorn

  7. Department of Hematology, Haga Hospital, The Hague, the Netherlands

    Paula F. Ypma

  8. Department of Internal Medicine, Ziekenhuis Gelderse Vallei, Ede, the Netherlands

    Gerjo A. Velders

  9. Department of Internal Medicine, Gelre Hospital, Zutphen, the Netherlands

    Leonie Strobbe

  10. Department of Internal Medicine-Hematology, Franciscus Hospital location Vlietland, Schiedam, the Netherlands

    Nazik Durdu-Rayman

  11. Department of Internal Medicine, Northwest Clinics, Alkmaar, the Netherlands

    Matthijs Westerman

  12. Department of Internal Medicine, Beatrix Hospital, Gorinchem, the Netherlands

    Marjan A. Davidis-van Schoonhoven

  13. Department of Internal Medicine/Hematology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands

    Roel J. W. van Kampen

  14. Department of Internal Medicine, MBA Spaarne Gasthuis, Hoofddorp, the Netherlands

    Aart Beeker

  15. Department of Internal Medicine, VieCuri Medical Center, Venlo, the Netherlands

    Ad Koster

  16. Department of Internal Medicine, St Jansdal Hospital, Harderwijk, the Netherlands

    Amanda C. Dijk

  17. Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands

    Ellen van der Spek

  18. Department of Hematology and Oncology, Maasstad Ziekenhuis, Rotterdam, the Netherlands

    Rineke B. L. Leys

  19. Department of Internal Medicine, Tergooi Hospital, Hilversum, the Netherlands

    Matthijs H. Silbermann

  20. Department of Internal Medicine, Bravis ziekenhuis, Roosendaal, the Netherlands

    Nicole C. H. P. van der Burg-de Graauw

  21. Department of Internal Medicine, Jeroen Bosch Ziekenhuis, ‘s Hertogenbosch, the Netherlands

    Harm A. M. Sinnige

  22. Department of Internal Medicine, Zaans Medical Center, Zaandam, the Netherlands

    Klaas G. van der Hem

  23. Department of Internal Medicine, Groene Hart Hospital, Gouda, the Netherlands

    Henriette Levenga

  24. Department of Internal Medicine, Admiraal de Ruijter Hospital, Goes, the Netherlands

    Yavuz M. Bilgin

  25. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands

    Pieter Sonneveld

  26. Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands

    Mark-David Levin

Authors
  1. Claudia A. M. Stege
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Corresponding author

Correspondence to Claudia A. M. Stege.

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Conflict of interest

NvdD has received research support from Janssen, Amgen, Celgene, Novartis, and BMS; and serves in advisory boards for Janssen, Amgen, Celgene, BMS, Takeda, Roche, Novartis, Bayer, and Servier. ISN serves in advisory boards for and received speakers fee from Celgene and Takeda. PS has received research support from and serves in advisory boards for Janssen, Takeda, Skyline Dx, Karyopharm and Amgen. MDL has received travel support from Janssen, Takeda and Roche, and serves in advisory boards for Takeda. SZ has received research funding from and has served in advisory boards for Celgene, Janssen and Takeda, Sanofi and Oncopeptids. Other authors have no conflicts of interest to report.

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Stege, C.A.M., Nasserinejad, K., Klein, S.K. et al. Improving the identification of frail elderly newly diagnosed multiple myeloma patients. Leukemia 35, 2715–2719 (2021). https://doi.org/10.1038/s41375-021-01162-z

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