Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma

Abstract

Heavy light chain (HLC) assays allow precise measurement of the monoclonal and of the noninvolved polyclonal immunoglobulins of the same isotype as the M‐protein (e.g., monoclonal IgAκ and polyclonal IgAλ in case of an IgAκ myeloma), which was not possible before. The noninvolved polyclonal immunoglobulin is termed ‘HLC‐matched pair’. We investigated the impact of the suppression of the HLC‐matched pair on outcome in 203 patients with multiple myeloma, a phenomenon that likely reflects the host's attempt to control the myeloma clone. Severe (>50%) HLC‐matched pair suppression was identified in 54.5% of the 156 newly diagnosed patients and was associated with significantly shorter survival (45.4 vs. 71.9 months, P = 0.019). This correlation was statistically significant in IgG patients (46.4 vs. 105.1 months, P = 0.017), but not in patients with IgA myelomas (32.9 vs. 54.1 months, P = 0.498). At best response, HLC‐matched pair suppression improved only in patients with ≥VGPR, indicating partial or complete humoral immune reconstitution during remission in those with excellent response. Severe HLC‐matched pair suppression retained its prognostic impact also during follow‐up after first response. In the 47 pretreated patients with relapsed/refractory disease, a similar correlation between severe HLC suppression and survival was noted (22.8 vs. not reached, P = 0.028). Suppression of the polyclonal immunoglobulins of the other isotypes than the myeloma protein correlated neither with HLC‐matched pair suppression, nor with outcome. Multivariate analysis identified severe HLC‐matched pair suppression as independent risk factor for shorter survival, highlighting the impact of isotype specific immune dysregulation on outcome in multiple myeloma. Am. J. Hematol. 91:295–301, 2016. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.

Serological normalisation as a surrogate marker for minimal residual disease negativity in multiple myeloma

“…The serological and bone marrow tests measured secreted protein and abnormal plasma cells, respectively. HLCr/FLCr analysis could indicate the functional output from residual healthy plasma cells, with recovery or preservation of polyclonal immunoglobulins improving outcomes in myeloma patients (Kastritis et al , ; Ludwig et al , ). Improved sensitivity of serological tests could result in a better correlation with MFC MRD testing.…”

Cytogenetic aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels

“…IgGκ/IgGλ). [6][7][8] As yet, the possible impact of CAs on Ig and FLC subtypes and their levels is poorly studied in MM.…”

Role of Suppressed Immunoglobulins in Outcome of Patients With Multiple Myeloma

“…Another similar study conducted by Pruzanski et al [9] showed that the degree of suppression of uninvolved immunoglobulins was related to worsened prognostic factors, but its effect on survival was not assessed. In contrast to the abovementioned papers, 2 studies [6,7] reported that the suppression of other isotypes (e g, IgA, or IgM for IgG-kappa myeloma) could not affect patients' outcome. Nonetheless, the level of uninvolved pair of monoclonal immunoglobulins (e g, IgG-lambda for IgG-kappa myeloma) was related to poorer survival.…”

“…The effect of suppression of uninvolved isotypes on the outcome of cases was previously studied and there was controversy in the results of the former works. In some studies, it was related to poorer outcome [3][4][5] and in others it did not affect patients' outcomes [6,7]. However, in previous studies the effect of treatment type on the outcome of cases was not evaluated concurrently.…”