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Multiple myeloma gammopathies

Impact of prior diagnosis of monoclonal gammopathy on outcomes in newly diagnosed multiple myeloma

Abstract

Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), or solitary plasmacytoma (SPC). There is a lack of data regarding impact of these pre-existing monoclonal gammopathies (MGs) on MM outcomes. Patients with prior diagnosis of MGUS, SMM, or PC from 1973 to 2015 (cases) were identified from our institution’s database and compared to those without a known MG (controls). The primary outcome of interest was overall survival (OS). Multivariate analysis was performed to ascertain factors impacting all-cause mortality. We identified 774 patients with a prior diagnosis of MGUS, SMM or SPC (cases) and a control population (1:2) matched for the year of diagnosis (n = 1548). After a median follow-up of 81 months, the cases showed a longer median OS than the controls (71 months vs. 56 months). The improved OS was limited to those with a known prior diagnosis of SMM (80 months) and SPC (95 months), compared to MGUS (60 months). Multivariable analysis revealed that MM patients with known prior MG had less overall mortality than those without, and this was limited to prior SMM/SPC group (HR 0.68, 95% CI: 0.50–0.93), as compared to the MGUS group (HR 0.83, 95% CI: 0.66–1.05).

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References

  1. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122–8.

    Article  CAS  Google Scholar 

  2. Kristinsson SY, Anderson WF, Landgren O. Improved long-term survival in multiple myeloma up to the age of 80 years. Leukemia. 2014;28:1346–8.

    Article  CAS  Google Scholar 

  3. Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113:5412–7.

    Article  CAS  Google Scholar 

  4. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. New Engl J Med. 2002;346:564–9.

    Article  Google Scholar 

  5. Go RS, Gundrum JD, Neuner JM. Determining the clinical significance of monoclonal gammopathy of undetermined significance: a SEER-Medicare population analysis. Clin Lymphoma Myeloma Leuk. 2015;15:177–186 e174.

    Article  Google Scholar 

  6. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354:1362–9.

    Article  CAS  Google Scholar 

  7. Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. New Engl J Med. 2007;356:2582–90.

    Article  CAS  Google Scholar 

  8. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.

    Article  Google Scholar 

  9. Sigurdardottir EE, Turesson I, Lund SH, Lindqvist EK, Mailankody S, Korde N, et al. The role of diagnosis and clinical follow-up of monoclonal gammopathy of undetermined significance on survival in multiple myeloma. JAMA Oncol. 2015;1:168–74.

    Article  Google Scholar 

  10. Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018;378:241–9.

    Article  CAS  Google Scholar 

  11. Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106:812–7.

    Article  CAS  Google Scholar 

  12. Bianchi G, Kyle RA, Colby CL, Larson DR, Kumar S, Katzmann JA, et al. Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications. Blood. 2010;116:2019–25.

    Article  CAS  Google Scholar 

  13. de Waal EG, Leene M, Veeger N, Vos HJ, Ong F, Smit WG, et al. Progression of a solitary plasmacytoma to multiple myeloma. A population-based registry of the northern Netherlands. Br J Haematol. 2016;175:661–7.

    Article  Google Scholar 

  14. Frassica DA, Frassica FJ, Schray MF, Sim FH, Kyle RA. Solitary plasmacytoma of bone: Mayo Clinic experience. Int J Radiat Oncol Biol Phys. 1989;16:43–8.

    Article  CAS  Google Scholar 

  15. Katodritou E, Terpos E, Symeonidis AS, Pouli A, Kelaidi C, Kyrtsonis MC, et al. Clinical features, outcome, and prognostic factors for survival and evolution to multiple myeloma of solitary plasmacytomas: a report of the Greek myeloma study group in 97 patients. Am J Hematol. 2014;89:803–8.

    Article  Google Scholar 

  16. Goyal G, Bartley AC, Funni S, Inselman J, Shah ND, Marshall AL, et al. Treatment approaches and outcomes in plasmacytomas: analysis using a national dataset. Leukemia. 2018;32:1414–20.

    Article  Google Scholar 

  17. Mateos MV, Hernandez MT, Giraldo P, de la Rubia J, de Arriba F, Corral LL, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. New Engl J Med. 2013;369:438–47.

    Article  CAS  Google Scholar 

  18. Ghobrial I, Caola A, Henrick P, Savell A, Cappuccio J, Rivotto B, et al. Phase II trial of combination of elotuzumab, lenalidomide, and dexamethasone in high-risk smoldering multiple myeloma. Haematologica. 2017;102:317–317.

    Article  Google Scholar 

Download references

Acknowledgements

This publication was made possible by CTSA Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.

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Contributions

GG and SK designed the study, performed statistical analysis and interpreted the data. GG wrote the paper with guidance from SK; SVR, MQL, MAG, FKB, AD, LH, AF, MH, SRH, SRZ, JAL, SJR, NL, PK, RSG, WIG, TK, RW and RAK critically reviewed the manuscript, and approved the final version. SK supervised the study.

Corresponding author

Correspondence to Shaji K. Kumar.

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Conflict of interest

MAG reports personal fees from Ionis/Akcea, Alnylam, Prothena, Celgene, Janssen, grants and personal fees from Spectrum, personal fees from Annexon, Appellis, Amgen, Medscape, Physicians Education Resource, personal fees for Data Safety Monitoring board from Abbvie, personal fees from Research to Practice, speaker fees from Teva, Speaker fees from Johnson and Johnson; Speaker fees from Medscape, Speaker fees DAVA oncology; Advisory Board for Pharmacyclics Advisory Board for Proclara outside the submitted work; Royalties from Springer Publishing Grant Funding Amyloidosis Foundation; grant from International Waldenstrom FoundationNCI SPORE MM SPORE 5P50 CA186781-04. SKK received consultancy from Celgene, Millennium, Onyx, Janssen, and BMS and research funding from Celgene, Millennium, Novartis, Onyx, AbbVie, Janssen, and BMS. MQL received research funding from Celgene. DD received research funding from Karyopharm Therapeutics, Amgen, and Millennium Pharmaceuticals. PK received research funding from Takeda, Sanofi, Janssen, Glaxo Smith Kline and Amgen. AD received research funding from Jannsen, Takeda, Celgene, Pfizer, Alnylam, Prothena, and GSK, and serves on the advisory board of Takeda and Intellia. NL serves on the advisory board of Takeda and Prothena. The remaining authors declare that they have no conflict of interest.

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Goyal, G., Rajkumar, S.V., Lacy, M.Q. et al. Impact of prior diagnosis of monoclonal gammopathy on outcomes in newly diagnosed multiple myeloma. Leukemia 33, 1273–1277 (2019). https://doi.org/10.1038/s41375-019-0419-7

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