Searching for a Connection Between Multiple Myeloma and Autoimmune Disease

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A number of studies have attempted to determine whether multiple myeloma is directly linked to autoimmune disease.
A number of studies have attempted to determine whether multiple myeloma is directly linked to autoimmune disease.

The term “autoimmune disease” encompasses a multitude of conditions, including systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and mixed connective tissue diseases. Up to 10% of the world's population is affected by autoimmune disease.

The underlying pathophysiology for each individual autoimmune disease is unique and complex, though a shared quality is an unregulated, hyperactive immune system that targets the patient's own body. This pro-inflammatory state could hypothetically serve as a nidus for developing cancer cells to flourish. There are studies proposing a link between autoimmune diseases and developing cancer; one such malignancy reported to have a link to autoimmune disease is multiple myeloma (MM).

Multiple myeloma is caused by the hyperproliferation of clonal plasma cells that accumulate in the bone marrow and secrete excess monoclonal proteins. Patients can present with hypercalcemia, renal dysfunction, bone pain, and anemia. B cells are the immune cell of origin in patients who develop MM.

There are numerous studies evaluating which autoimmune disease may be linked to MM. In one study, researchers reviewed data from over 400 patients with MM in Sweden who had 33 different autoimmune diseases.1 The overall standardized incidence ratio (SIR) for MM after any autoimmune disease 1.12; there was no impact on survival. The only 2 autoimmune diseases with significantly increased risk of MM were ankylosing spondylitis and systemic sclerosis. Rheumatic fever was the only autoimmune disease with a significant increase in hazard ratio.

There have also been studies evaluating the impact of familial history of autoimmune history and developing MM. One study evaluated first-degree relatives in Sweden and found that a family history of autoimmune disease was not associated with an increased risk of MM, but did carry an increased risk of 2 additional B cell malignancies, Hodgkin (HL) and non-Hodgkin lymphoma (NHL).2

Interestingly, 3 autoimmune diseases actually decreased the risk of developing HL (ankylosing spondylitis, acute glomerular nephritis, and Graves disease). Patients with first-degree relatives who had MM had an overall reduced SIR of autoimmune diseases.

MM is preceded by monoclonal gammopathy of undetermined significant (MGUS); some studies have attempted to evaluate the link between autoimmune diseases and this entity.3 A systematic review of 52 studies reported a 42% and 13% increased risk of MGUS and MM, respectively, in patients with “any autoimmune disorder.”4

The associations of autoimmune diseases and MM were stronger in studies conducted in Europe. Pernicious anemia was the only autoimmune disorder that increased the risk of both MM and MGUS. This study was limited, however, by the overall heterogeneity of the studies included in the analysis, a common theme when reviewing literature evaluating this potential association. The exact connection between autoimmune diseases and MGUS is therefore unknown.

RELATED: Elotuzumab Plus PVD for Relapsed Multiple Myeloma

There does appear to be a link between autoimmune diseases and MM, though further research is needed before conclusions can be drawn. Once more data are available, it would be interesting to evaluate if certain changes to modifiable risk factors, monitoring, treatment, and response could affect the development of MM in these patients.

References

  1. Hemminki K, Liu X, Försti A, Ji J, Sundquist J, Sundquist K. Effect of autoimmune diseases on incidence and survival in subsequent multiple myeloma. J Hematol Oncol. 2012;5:59. doi: 10.1186/1756-8722-5-59
  2. Hemminki K, Försti A, Sundquist K, Sundquist J, Li X. Familial associations of lymphoma and myeloma with autoimmune diseases. Blood Cancer J. 2017;7(1):e515. doi: 10.1038/bcj.2016.123
  3. Shimanovsky A, Alvarez Argote J, Murali S, Dasanu CA. Autoimmune manifestations in patients with multiple myeloma and monoclonal gammopathy of undetermined significance. BBA Clin. 2016;6:12-8. doi: 10.1016/j.bbacli.2016.05.004
  4. McShane CM, Murray LJ, Landgren O. Prior autoimmune disease and risk of monoclonal gammopathy of undetermined significance and multiple myeloma: a systematic review. Cancer Epidemiol Biomarkers Prev. 2014;23(2):332-42. doi: 10.1158/1055-9965.EPI-13-0695

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