Prognostic utility of intact immunoglobulin Ig′κ/Ig′λ ratios in multiple myeloma patients

Bradwell, Arthur R.; Harding, Stephen; Fourrier, N; Mathiot, Claire; Attal, Michel; Moreau, Philippe; Jl, Harousseau; Avet-Loiseau, Hervé

doi:10.1038/leu.2012.159

Cited by 67 publications

(102 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Measurements of these parameters were used to derive IgGκ/IgGλ and IgAκ/IgAλ ratios, which were compared with reference ranges 9, 10. HLC ratios outside of the reference ranges were considered to be indicative of a clonal process.…”

Section: Methodsmentioning

confidence: 99%

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

Ludwig

Milosavljevic

Berlanga³

et al. 2016

American J Hematol

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

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

Ludwig

Milosavljevic

Berlanga³

et al. 2016

American J Hematol

View full text Add to dashboard Cite

show abstract

“…[13][14][15] The results of these studies also provide additional biological insights into the pathogenesis of myeloma. Ludwig et al and Bradwell et al show that the diagnostic sensitivity for HLC-pair ratios in myeloma is comparable to PEL and IFE.…”

mentioning

confidence: 90%

A window into immunoglobulin quantitation and plasma cell disease: antigen epitopes defined by the junction of immunoglobulin heavy and light chains

Katzmann

Rajkumar

2013

Leukemia

View full text Add to dashboard Cite

“…HLC ratios were independently prognostic (P = 0.001), suggesting that HLC ratios may have a role in clinical management of MM. 24 Overall, a relatively higher HLC ratio of the uninvolved immunoglobulin is predictive of significantly longer PFS and OS in patients with MM in CR. Importantly, HLC ratios provide a composite measure of both tumor immunoglobulin production and immunoparesis rather than solely a measure of the malignant clone and MRD.…”

Section: Novel Biochemical Techniques For Serological Monitoring Of MMmentioning

confidence: 99%

“…Increased IgAκ/IgAλ and IgMκ/IgMλ ratios of the uninvolved isotype in patients with CR were associated with longer PFS (P = 0.006 and 0.01, respectively), with a statistical trend toward OS in the IgAκ/IgAλ group (P = 0.068). Bradwell et al 24 examined the prognostic significance of HLC subsets compared with monoclonal protein quantification by SPEP, SFLC and cytogenetic markers in 339 patients. Abnormal IgGκ/IgGλ and IgAκ/IgAλ ratios present in the respective tumor isotypes at clinical presentation were predictive of shorter PFS (HR: 1.9, P o0.001), predominantly owing to the suppression of the uninvolved (polyclonal) Ig of the same isotype as the tumor (HR: 1.8, P = 0.002).…”

Section: Novel Biochemical Techniques For Serological Monitoring Of MMmentioning

confidence: 99%

Minimal residual disease testing after stem cell transplantation for multiple myeloma

Sherrod

Hari

Mosse

et al. 2015

Bone Marrow Transplant

View full text Add to dashboard Cite

Prognostic utility of intact immunoglobulin Ig′κ/Ig′λ ratios in multiple myeloma patients

Cited by 67 publications

References 22 publications

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

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

A window into immunoglobulin quantitation and plasma cell disease: antigen epitopes defined by the junction of immunoglobulin heavy and light chains

Minimal residual disease testing after stem cell transplantation for multiple myeloma

Contact Info

Product

Resources

About