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Clinical impact of frailty on treatment outcomes of elderly patients with relapsed and/or refractory multiple myeloma treated with lenalidomide plus dexamethasone

International Journal of Hematology volume 113, pages 81–91 (2021)Cite this article

Abstract

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival.

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References

  1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–60.

    Article  CAS  Google Scholar 

  2. Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111:2962–72.

    Article  CAS  Google Scholar 

  3. Warren JL, Harlan LC, Stevens J, Little RF, Abel GA. Multiple myeloma treatment transformed: a population-based study of changes in initial management approaches in the United States. J Clin Oncol. 2013;31:1984–9.

    Article  CAS  Google Scholar 

  4. Bringhen S, Mateos MV, Zweegman S, Larocca A, Falcone AP, Oriol A, et al. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica. 2013;98:980–7.

    Article  Google Scholar 

  5. Cardoso AL, Fernandes A, Aguilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA, et al. Towards frailty biomarkers: candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res Rev. 2018;47:214–77.

    Article  CAS  Google Scholar 

  6. Larocca A, Dold SM, Zweegman S, Terpos E, Wäsch R, D’Agostino M, et al. Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN). Leukemia. 2018;32:1697–712.

    Article  Google Scholar 

  7. Sonneveld P. Management of multiple myeloma in the relapsed/refractory patient. Hematology. 2017;2017:508–17.

    Article  Google Scholar 

  8. Leng S, Bhutani D, Lentzsch S. How I treat a refractory myeloma patient who is not eligible for a clinical trial. Hematology. 2019;9:125–36.

    Article  Google Scholar 

  9. Moreau P, San Miguel J, Sonneveld P, Mateos M-V, Zamagni E, Avet-Loiseau H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv52–iv61.

    Article  CAS  Google Scholar 

  10. Dingli D, Ailawadhi S, Bergsagel PL, Buadi FK, Dispenzieri A, Fonseca R, et al. Therapy for relapsed multiple myeloma: guidelines from the mayo stratification for myeloma and risk-adapted therapy. Mayo Clin Proc. 2017;92:578–98.

    Article  Google Scholar 

  11. Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142–52.

    Article  Google Scholar 

  12. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.

    Article  CAS  Google Scholar 

  13. Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.

    Article  CAS  Google Scholar 

  14. Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621–34.

    Article  CAS  Google Scholar 

  15. Engelhardt M, Domm A-S, Dold SM, Ihorst G, Reinhardt H, Zober A, et al. A concise revised myeloma comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients. Haematologica. 2017;102:910–21.

    Article  Google Scholar 

  16. Engelhardt M, Dold SM, Ihorst G, Zober A, Möller M, Reinhardt H, et al. Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores. Haematologica. 2016;101:1110–9.

    Article  Google Scholar 

  17. Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen W-M, et al. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial. Leukemia. 2020;34:224–33.

    Article  Google Scholar 

  18. Palumbo A, Bringhen S, Mateos M-V, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125:2068–74.

    Article  CAS  Google Scholar 

  19. Jo J-C, Lee HS, Kim K, Lee J-J, Yoon S-S, Bang S-M, et al. The effectiveness and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma in real-world clinical practice: a study of the Korean Multiple Myeloma Working Party (KMMWP-151 study). Ann Hematol. 2020;99:309–19.

    Article  CAS  Google Scholar 

  20. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328–e346346.

    Article  Google Scholar 

  21. Gonsalves W, Leung N, Rajkumar SV, Dispenzieri A, Lacy M, Hayman S, et al. Improvement in renal function and its impact on survival in patients with newly diagnosed multiple myeloma. Blood Cancer J. 2015;5:e296.

    Article  CAS  Google Scholar 

  22. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015;33:2863–9.

    Article  CAS  Google Scholar 

  23. Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127:2955–62.

    Article  CAS  Google Scholar 

  24. Bringhen S, Offidani M, Palmieri S, Pisani F, Rizzi R, Spada S, et al. Early mortality in myeloma patients treated with first-generation novel agents thalidomide, lenalidomide, bortezomib at diagnosis: a pooled analysis. Crit Rev Oncol Hemat. 2018;130:27–35.

    Article  Google Scholar 

  25. Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–42.

    Article  CAS  Google Scholar 

  26. Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau J-L, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–32.

    Article  CAS  Google Scholar 

  27. Cook G, Larocca A, Facon T, Zweegman S, Engelhardt M. Defining the vulnerable patient with myeloma—a frailty position paper of the European Myeloma Network. Leukemia. 2020;1:10.

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank the Korean Multiple Myeloma Working Party and all the researchers and research nurses for their help in data collection and Sangjin Lee who analyzed data statistically. We would like to thank Editage (www.editage.co.kr) for English language editing.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea

    Ho Sup Lee

  2. Department of Medicine, Samsung Medical Center, Sunkyunkwan University School of Medicine, Seoul, South Korea

    Kihyun Kim

  3. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, South Korea

    Je-Jung Lee

  4. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

    Sung-Soo Yoon

  5. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea

    Soo-Mee Bang

  6. Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

    Jin Seok Kim

  7. Department of Internal Medicine, National Cancer Center of Korea, Goyang, South Korea

    Hyeon-Seok Eom

  8. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Dok Hyun Yoon

  9. Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, South Korea

    Yoojin Lee

  10. Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea

    Ho-Jin Shin

  11. Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea

    Yong Park

  12. Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea

    Yoojin Lee & Jae-Cheol Jo

  13. Department of Internal Medicine, Busan Paik Hospital, Busan, South Korea

    Won Sik Lee

  14. Department of Hemato-Oncology, Keimyung University Dongsan Medical Center, Daegu, South Korea

    Young Rok Do

  15. Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea

    Yeung-Chul Mun

  16. Division of Hematology-Oncology, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea

    Mark Hong Lee

  17. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea

    Hyo Jung Kim

  18. Department of Internal Medicine, Dong-A Medical Center, Dong-A University College of Medicine, Busan, South Korea

    Sung-Hyun Kim

  19. Department of Medicine, Yeungnam University College of Medicine, Daegu, South Korea

    Min Kyoung Kim

  20. Department of Internal Medicine, Haeundae Baek Hospital, Busan, South Korea

    Sung-Nam Lim

  21. Department of Hematology/Oncology, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea

    Seong Kyu Park

  22. Division of Hematology-Oncology, Department of Medicine, Chung-Ang University, Seoul, South Korea

    Jun Ho Yi

  23. Department of Internal Medicine, Gachon University Gil Hospital, Incheon, South Korea

    Jae Hoon Lee

  24. Department of Internal Medicine, Seoul St. Mary’s Hospital, Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea

    Chang-Ki Min

Authors
  1. Ho Sup Lee
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  2. Kihyun Kim
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  3. Je-Jung Lee
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  9. Yoojin Lee
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  15. Yeung-Chul Mun
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  16. Mark Hong Lee
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  22. Jun Ho Yi
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  23. Jae Hoon Lee
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  24. Chang-Ki Min
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Consortia

The Korean Multiple Myeloma Working Party (KMMWP)

Contributions

All authors had access to primary clinical trial data. This study was planned and led by Chang-Ki Min, written by Ho Sup Lee, and analyzed statistically by Sangjin Lee. Patient information was provided by the many investigators of the KMMWP. All authors were involved in manuscript preparation, which was led by Ho Sup Lee and Chang-Ki Min, and all authors approved the final version of the manuscript.

Corresponding author

Correspondence to Chang-Ki Min.

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Conflict of interest

The authors declare that there are no conflicts of interest. No funding was received for this study.

Ethical approval

According to the Declaration of Helsinki, the trial was approved by the Institutional Research Ethics Board of Kosin University Gospel Hospital, which waived the requirement for informed consent given the retrospective nature of this study (IRB approval number 2020–01-005).

Ethical standards

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

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Lee, H.S., Kim, K., Lee, JJ. et al. Clinical impact of frailty on treatment outcomes of elderly patients with relapsed and/or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Int J Hematol 113, 81–91 (2021). https://doi.org/10.1007/s12185-020-02988-6

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  • DOI: https://doi.org/10.1007/s12185-020-02988-6

Keywords

  • Elderly multiple myeloma
  • Relapsed and refractory
  • Lenalidomide and dexamethasone
  • Frailty
  • Survival