Levels of uninvolved immunoglobulins predict clinical status and progression‐free survival for multiple myeloma patients

Harutyunyan, Nika Manik; Vardanyan, Suzie; Ghermezi, Matthew; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R.

doi:10.1111/bjh.14026

Cited by 19 publications

(31 citation statements)

References 20 publications

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“…The HevyLite assay has been used to help identify the involved Ig, but it still does not specifically identify the paraprotein within all of the matching isotype pairs. 35 Notably, the serum half-life of Ig is also long, 36,37 so that real-time measurements do not necessarily reflect current disease activity. More recently, the measurement of SFLC levels has been used; its levels and ratios and differences between the involved and uninvolved light chains are useful for monitoring and predicting outcomes for MM patients.…”

Section: Introductionmentioning

confidence: 99%

Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients

et al. 2016

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B-cell maturation antigen is expressed on plasma cells. In this study, we have identified serum B-cell maturation antigen as a novel biomarker that can monitor and predict outcomes for multiple myeloma patients. Compared to healthy donors, patients with multiple myeloma showed elevated serum B-cell maturation antigen levels (P<0.0001). Serum B-cell maturation antigen levels correlated with the proportion of plasma cells in bone marrow biopsies (Spearman’s rho = 0.710; P<0.001), clinical status (complete response vs. partial response, P=0.0374; complete response vs. progressive disease, P<0.0001), and tracked with changes in M-protein levels. Among patients with non-secretory disease, serum B-cell maturation antigen levels correlated with bone marrow plasma cell levels and findings from positron emission tomography scans. Kaplan-Meier analysis demonstrated that serum B-cell maturation antigen levels above the median levels were predictive of a shorter progression-free survival (P=0.0006) and overall survival (P=0.0108) among multiple myeloma patients (n=243). Specifically, patients with serum B-cell maturation antigen levels above the median level at the time of starting front-line (P=0.0043) or a new salvage therapy (P=0.0044) were found to have shorter progression-free survival. Importantly, serum B-cell maturation antigen levels did not show any dependence on renal function and maintained independent significance when tested against other known prognostic markers for multiple myeloma such as age, serum β2 microglobulin, hemoglobin, and bone disease. These data identify serum B-cell maturation antigen as a new biomarker to manage multiple myeloma patients.

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Section: Introductionmentioning

confidence: 99%

Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients

et al. 2016

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“…Limited studies previously examined the effect of immunoglobulins suppression on patients' outcome and as mentioned before, there were biases on the results of their works. Based on the studies by Kastritis et al, [3] and Harutyunyan et al [4], immunoglobulin suppression was associated with poorer survival. In the study by Sari et al [5], suppression of uninvolved immunoglobulins was related to lower survival, although the findings were not statistically significant.…”

Section: Discussionmentioning

confidence: 97%

“…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.…”

Section: Introductionmentioning

confidence: 99%

Role of Suppressed Immunoglobulins in Outcome of Patients With Multiple Myeloma

Jalaeikhoo

Rajaeinejad

Keyhani

et al. 2017

mcij

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Introduction: Multiple myeloma (MM) is typically presented with abundant monoclonal secretion of one type of immunoglobulin. The other classes of immunoglobulins, which are uninvolved and not secreted by malignant plasma cells, could be decreased. A number of previous studies reported the effect of suppression of uninvolved immunoglobulins on the outcome of patients with myeloma. However, its effect in regard to the type of treatment was not studied so far. The current study aimed at investigating the effect of uninvolved immunoglobulins suppression on the outcome of patients with myeloma in each individual type of treatment. Methods: In the current retrospective study, 140 myeloma cases diagnosed from 1999 to 2016 were studied. Patients were divided into 2 groups according to the first-line chemotherapy: 58 cases treated with Velcade-based and 81 cases with other agents. In the 2 groups, the effects of immunoglobulin suppression as well as other prognostic parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. Results: The effect of immunoglobulin suppression on patients' outcome depended on the type of treatment. In the Velcade group, suppression of at least 2 classes of immunoglobulins was significantly related to poorer survival in terms of both OS and PFS. In the non-velcade group, suppression of immunoglobulins showed no significant relationship with OS or PFS. Conclusions: For cases treated with Velcade, suppression of 2 types of immunoglobulins was related to poorer outcomes. Based on the results of the current study, it seemsed that immunoglobulin suppression was a predictive factor rather than a prognostic one. More studies with a larger sample size should be conducted to assess the outcome of patients treated with Velcade and severely suppressed immunoglobulins.

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“…For example, an IgA MGUS or SMM has a four times higher risk of progressing to PCM than other subtypes [44], whilst IgD PCM has been associated with poorer outcomes. Suppression of Ig subtypes other than the subtype of the plasma cell clone is also associated with an increased risk of progression from precursor to PCM [44], and with clinical status and progression-free survival (PFS) in PCM [45]. Paraprotein identification in MGUS allows categorisation into IgM, non-IgM and light chain MGUS, which are clinically distinct conditions [7].…”

Section: Risk Stratificationmentioning

confidence: 99%

Towards Stratified Medicine in Plasma Cell Myeloma

Egan¹,

Drain²,

Conway³

et al. 2016

IJMS

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Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient’s age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies. Clinical staging, recurring acquired cytogenetic aberrations, and serum biomarkers such as β-2 microglobulin, and free light chains are in widespread use but often fail to predict the disease progression or inform treatment decision making. Recent scientific advances have provided considerable insight into the biology of myeloma. For example, gene expression profiling is already making a contribution to enhanced understanding of the biology of the disease whilst Next Generation Sequencing has revealed great genomic complexity and heterogeneity. Pathways involved in the oncogenesis, proliferation of the tumour and its resistance to apoptosis are being unravelled. Furthermore, knowledge of the tumour cell surface and its interactions with bystander cells and the bone marrow stroma enhance this understanding and provide novel targets for cell and antibody-based therapies. This review will discuss the development in understanding of the biology of the tumour cell and its environment in the bone marrow, the implementation of new therapeutic options contributing to significantly improved outcomes, and the progression towards more personalised medicine in this disorder.

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Levels of uninvolved immunoglobulins predict clinical status and progression‐free survival for multiple myeloma patients

Cited by 19 publications

References 20 publications

Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients

Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients

Role of Suppressed Immunoglobulins in Outcome of Patients With Multiple Myeloma

Towards Stratified Medicine in Plasma Cell Myeloma

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