Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment

Sugihara, Hiroyuki; Chihara, Dai; Seike, Keisuke; Fukumoto, Kota; Fujisawaa, M; Suehara, Yasuhito; Nishida, Yuhki; Takeuchi, Masami; Matsue, Kosei

doi:10.1038/bcj.2014.56

Cited by 7 publications

(8 citation statements)

References 31 publications

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“…Explanatory variables: age, 46–48,60,61,63–71,74,77,80 serum LDH level, 46,51,62,64,65,73,76,79–81,88 light chains level, 44,46–54 β 2 microglobulin level, 51,62,64,70,71,79–81,89,90 albumin level, 53,64–66,71,79,80 M protein level, 59,70,91–93 t(14), 55–59 pain, 69,83,85,…”

Section: Resultsmentioning

confidence: 99%

“…Numbers in brackets are the number of attributes in each group. In total, 56 MM attributes were identified as significant, that is, those that have a significant relationship with another attribute; these were grouped into five categories: disease characteristics, 44–54 cytogenetic factors, 55–59 patient characteristics, 45–48,51,53,55,60–81 QoL, 69,75,82,83 and symptoms. 46,69,71,82–87 …”

Section: Resultsmentioning

confidence: 99%

“…BAFF, B-cell activating factor; BLyS, B-lymphocyte stimulator; BMI, body mass index; CCND1, gene encoding cyclin D1; CD81, gene encoding cluster of differentiation 81; ECOG, Eastern Cooperative Oncology Group; ESR, erythrocyte sedimentation rate; FACT-MM, Functional Assessment of Cancer Therapy-Multiple Myeloma; HRQoL, health-related quality of life; IL, interleukin; IRF4, gene encoding interferon regulatory factor 4; ISS, International Staging System; LDH, lactate dehydrogenase; MDR1, multidrug resistance gene 1; MIP-1a, macrophage inflammatory protein 1a; MKI67, gene encoding marker of proliferation Ki-67; MM, multiple myeloma; QoL, quality of life; RBC, red blood cell; sFAS-L, soluble Fas ligand; sFLCR, serum free light-chain ratio.Numbers in brackets are the number of attributes in each group. In total, 56 MM attributes were identified as significant, that is, those that have a significant relationship with another attribute; these were grouped into five categories: disease characteristics,[44][45][46][47][48][49][50][51][52][53][54] cytogenetic factors,[55][56][57][58][59] patient characteristics,[45][46][47][48]51,53,55, QoL,69,75,82,83 and symptoms 46,69,71,[82][83][84][85][86][87].…”

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confidence: 99%

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Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making

Gonzalez‐McQuire

Dimopoulos

Weisel

et al. 2019

MDM Policy & Practice

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Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confirm the relationships between attributes using pairwise correlations and multiple Cox regression analysis. Results. The Delphi panel reached consensus that most cytogenetic abnormalities influenced disease activity, which results in symptoms and complications and affects overall survival (OS). Comorbidities and complications also affect OS. The entire panel agreed that quality of life was influenced by comorbidities, age, complications, and symptoms. Consensus was not reached in some cases, in particular, the influence of del(17p) on complications. The relationships between attributes were confirmed using pairwise analysis of real-world data from the Czech RMG; most of the correlations identified were statistically significant and the strength of the correlations changed with successive relapses. Czech RMG data were also used to confirm significant predictors of OS included in the model, such as age, Eastern Cooperative Oncology Group performance status, and extramedullary disease. Conclusions. This validated conceptual model can be used for economic modeling and clinical decision making. It could also inform the development of disease-based models to explore the impact of disease progression and treatment on outcomes in patients with MM.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making

Gonzalez‐McQuire

Dimopoulos

Weisel

et al. 2019

MDM Policy & Practice

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“…11,19 In relation to these results, we previously reported that the percentage of urinary albumin excreted reflects the pathogenesis of RI and predicted renal response in myeloma patients. 20 However, some patients continue to develop severe RI, despite novel anti-myeloma therapy and the achievement of early FLC reduction. In patients receiving novel agents, an additional factor, which can indicate the reversibility of RI, remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Association between serum erythropoietin levels and renal reversibility in patients with renal impairment from multiple myeloma

et al. 2020

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Renal impairment (RI) is a common clinical presentation in patients with multiple myeloma (MM). Despite treatment with novel agents or management strategies that focus on the disease response, some patients develop irreversible RI. This study aimed to determine the influencing, clinical variables of renal reversibility in patients with RI treated with novel drugs. We analyzed 244 patients newly diagnosed with MM retrospectively. Maximum renal response was assessed according to the criteria for the definition of renal response proposed by the International Myeloma Working Group. Major renal response was defined as the occurrence of complete renal response or partial renal response. RI (a glomerular filtration rate < 50 mL/min/1.73 m2) was observed in 110 patients (45%). In total, 56 patients (51%) achieved a major renal response. Serum erythropoietin (EPO) levels >25 mIU/mL (P < .001) and a percentage of urinary albumin excretion ≤25% (P < .001) were both significant factors that influenced the occurrence of major renal responses. Both remained significant factors associated with renal reversibility in the multivariate analysis. Patients were assigned a score of 1 each for EPO >25 mIU/mL and urinary albumin ≤25%. The estimated 6‐month rates of major renal responses of patients with scores of 2, 1, and 0 were 78.6%, 30.6%, and 0%, respectively (P < .001). In conclusion, a serum EPO level >25 mIU/mL is an independent predictive factor for major renal response and may predict renal reversibility more accurately when urinary albumin level is congruently ≤25%.

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“…Hutchison et al [13] in their study on 39 patients with biopsy proven myeloma kidney, had found a linear relationship between FLC reduction and renal recovery, with a 60% reduction in FLC by day 21 being associated with renal recovery for 80% of the population. A retrospective analysis of 279 patients by Sugihara et al [14] have found that reduction of iFLC 95% at day 21 (P = 0.015) and urinary albumin ≦ 25% (P = 0.007) was significant for any renal response in patients with myeloma kidney. In our study, we found that 84% reduction in iFLC value was associated with renal recovery with a sensitivity and specificity of 77.7% and 75% respectively.…”

Section: Discussionmentioning

confidence: 99%

Day 21 serum Free Light Chain (FLC) levels as a predictor of response to therapy in symptomatic multiple myeloma

Langer

Mulam

2021

Curr Cancer Rep

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Introduction: Serum Free Light Chain (sFLC) assay has a major role in the screening, diagnosis and monitoring in patients with Multiple Myeloma (MM). Measuring involved Free Light Chain (iFLC) has a proven advantage due to the short half-life compared to that of M-protein, thus useful as a prognostic tool for the assessment of response to therapy. It is established that achieving VGPR (very good partial response) or better after induction chemotherapy is associated with better OS (overall survival) and PFS (progression free survival) in myeloma patients. Few studies have shown that early reduction in iFLC during treatment is associated with achievement of VGPR or better. Objective: To study the predictive value of reduction of involved free light chain level on Day 21 of chemotherapy for achievement of VGPR after 4 cycles of induction chemotherapy. Methods: We conducted a prospective observational study in twenty eight patients of newly diagnosed Multiple Myeloma with iFLC ≥ 100mg/L. Serum FLC assay was done at baseline and on day 21 of therapy. All patients were followed up till the end of induction therapy for response assessment based on the IMWG criteria. Receiver Operator Characteristic (ROC) curve analysis was done to determine the cut off value of percent reduction in day 21 iFLC for achievement of VGPR or better. Results: After the induction chemotherapy, out of 28 patients, 13 patients achieved CR, 8 patients achieved VGPR, 4 patients achieved PR and 2 patients had stable disease (≥ VGPR = 21 patients, < VGPR = 6 patients). One patient expired after 2nd cycle of chemotherapy. The mean per cent reduction in day 21 iFLC level as compared to baseline was 91.5% and 57.1% in patients achieving ≥ VGPR and < VGPR (P < 0.0001), respectively. No other baseline parameter was found to be significantly different between the 2 groups. ROC curve analysis demonstrated a cut off of 84% reduction in iFLC value on day 21 (AUC of 0.937) had a sensitivity of 85.7% and a specificity of 100% in predicting the achievement of VGPR after four cycles of induction chemotherapy. Conclusion: Monitoring iFLC levels on Day 21 can be used as an important tool for early identification of responders/non responders to myeloma therapy. We recommend serum FLC assay to be done on day 21 as a real time assessment of treatment response in newly diagnosed myeloma patients. Key words- Multiple Myeloma, involved Free Light Chain (iFLC), Very Good Partial Response (VGPR)

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Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment

Cited by 7 publications

References 31 publications

Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making

Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making

Association between serum erythropoietin levels and renal reversibility in patients with renal impairment from multiple myeloma

Day 21 serum Free Light Chain (FLC) levels as a predictor of response to therapy in symptomatic multiple myeloma

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