Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma

Koulieris, Efstathios; Panayiotidis, Panayiotis; Harding, Stephen; Kafasi, Nikolitsa; Maltezas, Dimitrios; Bartzis, Vassiliki; Τζένου, Τατιάνα; Dimou, Maria; Georgiou, George; Mirbahai, Ladan; Bradwell, Arthur R.; Kyrtsonis, Marie‐Christine

doi:10.1186/2162-3619-1-9

Cited by 40 publications

(48 citation statements)

References 17 publications

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“…Previously, we 15 and others 33 have shown a close correlation of a highly abnormal HLC ratio with short survival. In this study, we showed that this applies to patients with relapsed/refractory disease as well.…”

Section: Discussionmentioning

confidence: 54%

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

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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.

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Section: Discussionmentioning

confidence: 54%

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

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“…Unlike most studies reporting abnormal HLC-r values in all MM patients [2][3]12 , this study showed the same result in the IgA-κ type of MM only; the other results were 98% for IgG-κ, 97% for IgG-λ and 92% for IgA-λ, suggesting that detection of a normal HLC-r does not rule out the diagnosis of MM in all cases 16 . Correlation analysis showed only slightly significant relationship between HLC-r (Hevylite TM ) and FLC-r (Freelite TM ) indices in the IgG MM group, both in IgG-κ and -λ isotypes, but there was no significance in the IgA group.…”

Section: Discussioncontrasting

confidence: 44%

“…In the pilot study the analysis aimed at high values of both HLC-r and FLC-r, there were correlations for both IgG and IgA types of MM (ref. 12 ). The biological variability of FLC-κ and FLC-λ demonstrates significant relationship of HLC-r index to the levels of FLC-λ, but not to FLC-κ in IgG-κ and IgG-λ types of MM.…”

Section: Discussionmentioning

confidence: 99%

“…Spearman correlation analysis in our study showed significant correlation between x HLC-r values and Hb in IgG-κ and -λ type, confirmed using Mann-Whitney test in the groups with Hb cut off level both < 120 and < 100 g/L only in IgG type, whereas Koulieris et al reported different correlations of i-HLC and high HLC-r with Hb in both the IgG and IgA types of MM (ref. 12 ). In agreement with our results, a significant association between HLC and severity of anemia was described in Waldenström macroglobulinemia, with the median IgM i-HLC being significantly higher in patients with Hb < 100 g/L (ref.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to separate measurements of serum levels of the IgG-κ and -λ, IgA-κ and -λ, and IgM-κ and -λ pairs, Hevylite TM may be used to calculate the HLC-r, that is, the ratio of the monoclonal i-HLC/u-HLC Ig pairs (HLC-κ /HLC-λ and HLC-λ/HLC-κ) (ref. 2,7,8,[10][11][12][13][14] ). Given the still unresolved role of Hevylite TM in clinical practice and only sporadic studies on the association be- n -number of patients, Md -median, FLC -serum immunoglobulin free light chains, HLC -immunoglobulin heavy/light chain pairs, HLC-r -HLC-κ/HLC-λ ratio,…”

Section: Introductionmentioning

confidence: 99%

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Relationship of differences in immunoglobulin heavy/light chain pairs (Hevylite<sup>TM</sup>), selected laboratory parameters and stratification systems in different immunochemical types of multiple myeloma

Scudla¹,

Lochman²,

Pika³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background and Aims. Advances in the diagnosis and treatment of multiple myeloma (MM), place increasing demands on accurate stratification of patients as the starting point for optimal individualized therapy. The present study focused on assessing the association between HLC levels and the HLC-r to parameters of MM activity, prognosis and tumor mass volume.The objective was to assess the correlation of immunoglobulin (Ig), heavy/light chain (HLC) pairs (IgG-κ and-λ, IgA-κ and -λ HLC) and the ratio of monoclonal involved-HLC (i-HLC) to polyclonal uninvolved (u-HLC) Ig concentrations assessed by the Hevylite TM method with the free light chain κ/λ ratio (FLC-r), selected prognostic laboratory parameters i.e. Hb, platelets, albumin, β 2 -microglobulin (β 2 -M), Ca, lactate dehydrogenase (LDH), creatinine and the Durie-Salmon (D-S) and International Staging System (ISS), stages (1-3) for MM. Methods. Hevylite TM assays were done on the sera of 132 MM patients at the time of diagnosis (IgG 94, IgA 38). HLC-r was calculated in the case of i-HLC-κ from the i-HLC-κ/u-HLC-λ ratio and for i-HLC-λ from the i-HLC-λ/u-HLC-κ ratio. D-S and ISS stages were evenly distributed. Results. Md IgG-κ HLC-r was 64.8 (2.7-2222) and of IgG-λ HLC-r 49.6 (0.7-465.1), in the case of IgA-κ, Md HLC-r was 408.9 (3.4-3966) and for IgA-λ HLC-r the Md was 180.0 (0.1-3110). Normal levels of HLC pairs and HLC-r did not always rule out the diagnosis of MM. HLC-r correlated with FLC-r in IgG (r = 0.244, P = 0.018), but not in the IgA type. For IgG, HLC-r values were significantly different in patients with abnormal vs normal levels of Hb (P < 0.0001), albumin (P < 0.043), β 2 -M (P < 0.0001) and creatinine (P = 0.034) but not thrombocyte count, Ca or LDH. For the IgA isotype, we found a significant difference in HLC-r values only for thrombocyte count (P = 0.026) and β 2 -M (P = 0.016) but not for Hb, albumin, Ca, LDH or creatinine. For the IgG isotype there was a significant relationship of HLC-r index to stages 1-3 (P = 0.038) and substage A vs B (P = 0.048) according to D-S, and with high significance to stages 1-3 according to ISS (P = 0.005) and between stages 1 vs 3 (P = 0.001). For the IgA isotype, we found significant differences in HLC-r only between stages 1-3 (P = 0.025) according to D-S but not in the case of ISS. There were no significant correlations between i-HLC Ig levels and D-S or ISS stages in both IgG-κ and λ and IgA-κ and λ. Exceptions were significant differences for stages 1 vs 3 (P = 0.012) and 2 vs 3 (P = 0.017) for the IgG-λ isotype. There were no correlations of the HLC-r and u-HLC levels for either D-S or ISS stratifications in all HLC isotypes. Conclusion. We found a significant positive contribution of HLC-r using the i-HLC/u-HLC ratio even in the case of i-HLC-λ i.e. i-HLC-λ/u-HLC-κ. Variable results for the relationship of important laboratory parameters and D-S and ISS stratifications (stage 1-3) to HLC-r values in IgG and IgA isotypes make separate interpretation of the Hevylite TM method results necessary in clinic...

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Risk Stratification in Multiple Myeloma

Ooi¹,

Mel

Chng

2016

Curr Hematol Malig Rep

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There are many prognostic variables in multiple myeloma and the difficulty is in deciding which is truly significant. The widely used International Staging System (ISS) does not incorporate genetics, age, and other important variables in its risk stratification. Although it has its own limitations, the recently published Revised International Staging System (R-ISS) that was built upon the framework of ISS, is a more comprehensive and predictive tool for multiple myeloma patients and should be henceforth utilised. We will review the current prognostic variables and their significance in this paper.

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Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma

Cited by 40 publications

References 17 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

Relationship of differences in immunoglobulin heavy/light chain pairs (Hevylite<sup>TM</sup>), selected laboratory parameters and stratification systems in different immunochemical types of multiple myeloma

Risk Stratification in Multiple Myeloma

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