Abstract
We measured immunosuppression at myeloma diagnosis and assessed the impact on survival in 5826 UK myeloma trial patients. Polyclonal immunoglobulin levels were below normal in 85% of patients and above normal in only 0.4% of cases for IgA, 0.2% for IgM and no cases for IgG. Immunoparesis had a greater impact in recent trials: median overall survival (OS) was up to 3 years longer for patients without immunoparesis compared to the old trials, less than 1 year longer. Median progression-free survival (PFS) was 39%, 36% and 57% longer for patients with normal IgG, IgA and IgM levels, respectively. The depth of IgM suppression, but not the depth of IgG or IgA suppression, was prognostic for survival: the most severely suppressed IgM tertile of patients OS was 0.9 years shorter than those in the top tertile, and 2.6 years shorter than OS of those with normal IgM levels (p = .007). The degree of suppression of polyclonal IgM levels below normal was associated with worse PFS (p = .0002). Infection does not appear to be the main mechanism through which immunoparesis affects survival. We hypothesise that IgM immunoparesis impacts through a combination of being associated with more aggressive disease and reduced immune surveillance against relapse.
Highlights
MethodsPatients and clinical trialsPatients were enroled in either the MRC Myeloma IX (MIX) trial (ISRCTN68454111) or the Cancer Research UKMyeloma XI (MXI) trial (ISRCTN49407852), and will be referred to as the ‘recent myeloma trials’
Survival outcomes were analysed between patients who were below or within the normal range (NR) for polyclonal immunoglobulins and FLCs, and assessed based on the degree of immunoparesis
Degree of immunoparesis was obtained by splitting the patients who were below the NR into three groups for IgG, IgA and IgM individually
Summary
Patients and clinical trialsPatients were enroled in either the MRC Myeloma IX (MIX) trial (ISRCTN68454111) or the Cancer Research UKMyeloma XI (MXI) trial (ISRCTN49407852), and will be referred to as the ‘recent myeloma trials’. Only the data on 3218 out of the 3247 patients, where polyclonal IgM was recorded as part of the central laboratory immunochemistry analysis, were included in the patient characteristics table and multivariate analysis To compare these trials using current anti-myeloma therapy to trials pre-dating novel biological agents, data were included from 2807 patients who enroled in MRC myeloma trials (MIV, MV, MVI and MVIII) from 1980 to 1997, referred to as the ‘old’ myeloma trials. Treatment allocation within these trials has been described previously [23]. Multicentre research ethics committees and local ethics committees approved all the trials, and all patients gave written informed consent
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