Protein Z in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4518-4518
Author(s):  
Jolanta Oleksiuk ◽  
Janusz Kloczko ◽  
Ewa Luksza ◽  
Marzenna Galar
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Plasma Levels ◽  
Serum Immunoglobulin ◽  
Disease Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Newly Diagnosed ◽  
Protein Z ◽  
Coagulation Abnormalities

Abstract Background Patients with multiple myeloma (MM) are relatively high risk of developing thromboembolic events. The pathogenesis of prothrombotic coagulation abnormalities in MM is not clear and probably of multifactorial origin. The deficiency of natural anticoagulant mechanisms, acquired resistance to protein C and reduced protein S function, has been described as one of the possible reason of hypercoagulable state in MM patients. Protein Z/Z-dependent protease inhibitor (PZ/ZPI) is a new anticoagulant system has been recently describe. PZ is a vitamin K-dependent protein which serves as cofactor for the ZPI that inactivates activated factor X, XI and IX by different mechanisms. Some reports suggest that protein Z deficiency might imbalance the haemostatic system with thrombotic consequences. However, to the best of our knowledge, no data are available regarding the potential role of protein Z in prothrombotic coagulation abnormalities in MM. Aim: The aim of our study was to evaluate the plasma concentration of protein Z in relation to disease stage, type and levels monoclonal protein in patients with newly diagnosed untreated multiple myeloma. Methods: The study population consisted of 41 patients (25 male, 16 female; median age: 63 years) with newly diagnosed untreated multiple myeloma. The presence of monoclonal serum immunoglobulin was found in 33 patients (25 and 8 with IgG and IgA paraprotein, respectively). The disease stage was evaluated according to Durie and Salmon criteria: 4 patients-stage I, 28 patients-stage II and 19 patients-stage III; in 8 of them abnormal renal function (serum creatinine value ≥2.0 mg/dl) was observed. The control group was formed by 19 healhty individuals with age and sex comparable with the patients. Protein Z plasma levels were measured using a commercial enzyme-linked immunosorbent assay (Asserachrom Protein Z; Diagnostica Stago, Asnieres) following the manufacturer’s instruction. Results: The median protein Z plasma levels in patients with multiple myeloma and control subjects were similar. Median PZ levels were 1.45 ug/ml (range 0.27–3.17 ug/ml) in patients and 1.37ug/ml (range 0.34–1.96 ug/ml) in controls (p≥0.05). No significant correlation was found between protein Z plasma levels and disease stage, monoclonal serum immunoglobulin concentration, and renal function as well. Conclusions: Our results suggest that protein Z is not an independent risk factor for thrombosis and does not play a significant role in the mechanism of thrombotic complication in patients with multiple myeloma.

scholarly journals Circulating Soluble Urokinase-Type Plasminogen Activator Receptor Levels Reflect Renal Function in Newly Diagnosed Patients with Multiple Myeloma Treated with Bortezomib-Based Induction

2020 ◽  
Vol 9 (10) ◽  
pp. 3201
Author(s):  
Evangelos Terpos ◽  
Ioannis Ntanasis-Stathopoulos ◽  
Gerasimos-Petros Papassotiriou ◽  
Efstathios Kastritis ◽  
Alexandra Margeli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Plasminogen Activator ◽  
Disease Stage ◽  
Newly Diagnosed ◽  
Best Response ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Before And After ◽  
Plasminogen Activator Receptor

(1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p < 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA < 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p < 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR < 50 mL/min/1.73 m2. (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response.

PP455 Cost-effectiveness Of Ixazomib-Based Regimen Compared With Bortezomib-Based Regimen In Chinese Patients With Relapsed/Refractory Multiple Myeloma: A Retrospective Study

2020 ◽  
Vol 36 (S1) ◽  
pp. 36-37
Author(s):  
Pei Wang ◽  
Jing Li ◽  
Yang Yang ◽  
Peng Liu
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Staging System ◽  
Chinese Patients ◽  
Disease Stage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lower Grade ◽  
Refractory Multiple Myeloma ◽  
Grade 3

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

scholarly journals Plasma Level of MMP-10 May Be a Prognostic Marker in Early Stages of Breast Cancer

2020 ◽  
Vol 9 (12) ◽  
pp. 4122
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Area Under The Curve ◽  
Disease Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Early Stages ◽  
Potential Marker ◽  
Breast Cancer Biomarkers ◽  
Diagnostic Usefulness ◽  
Chemiluminescent Microparticle Immunoassay

Background: Stromelysins are potential breast cancer biomarkers. The aim of the study was to evaluate if plasma levels of selected metalloproteinases (MMPs) (stromelysin-1 (MMP-3) and stromelysin-10 (MMP-10)) and cancer antigen 15-3 (CA 15-3) used separately and in combination demonstrated diagnostic usefulness in breast cancer (BC). Methods: The study group consisted of 120 patients with BC, while the control group included 40 patients with benign breast cancer and 40 healthy individuals. Concentrations of MMP-3 and MMP-10 were determined by enzyme-linked immunosorbent assay; CA 15-3 was determined by chemiluminescent microparticle immunoassay. Results: In the group of patients with BC, the area under the curve (AUC) was significantly higher for all markers (except MMP-3) and all sets of markers. At the earliest disease stage, only MMP-10 had a significantly higher AUC (AUC = 0.8692, p < 0.001). Moreover, MMP-10 had the highest AUC (0.9166) among parameters tested separately. The highest AUC was observed for the combination of MMP-10 + CA 15-3 and MMP-3 + MMP-10 + CA 15-3 in line with disease progression (stage I 0.8884 and 0.8906, stage II 0.9244 and 0.9308, stages III + IV 0.9919 and 0.9944, respectively, p < 0.001 in all cases). Conclusions: The results suggest that MMP-10 could be a potential marker in early stages of BC. Moreover, plasma concentration of MMP-10 and MMP-3 in combination with CA 15-3 may improve diagnosis of this type of cancer.

scholarly journals Role of interleukin-10 and interleukin-24 in the pathogenesis of В-cell chronic lymphocytic leukemia

2018 ◽  
pp. 56-61
Author(s):  
Т.Н. Жевак ◽  
Н.П. Чеснокова ◽  
Т.В. Шелехова ◽  
О.Е. Царева ◽  
И.А. Будник ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Serum Level ◽  
B Cell ◽  
Serum Levels ◽  
Lymphocytic Leukemia ◽  
Disease Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Patient Groups ◽  
Cell Chronic Lymphocytic Leukemia

Цель. Изучить закономерности изменения экспрессии интерлейкина-10 и интерлейкина-24, обладающих иммуномодулирующим эффектом, при развитии B-клеточного хронического лимфолейкоза. С учетом этого выявить информативные прогностические критерии развития гемобластоза и/или нового подхода к терапии заболевания. Методы. У 120 больных с разными стадиями В-клеточного хронического лимфолейкоза методом твердофазного иммуноферментного анализа исследована динамика уровней интерлейкина-10 и интерлейкина-24 в сыворотке крови. Результаты. Обнаружено закономерное повышение содержания интерлейкина-10 и интерлейкина-24 в сыворотке крови пациентов уже на начальной стадии B-клеточного хронического лимфолейкоза и сохранение их достоверно высоких уровней на последующих стадиях заболевания. Заключение. Обнаруженный нами факт повышения содержания интерлейкина-10 в сыворотке крови пациентов с В-клеточным хроническим лимфолейкозом является фактором риска снижения противоопухолевой защиты организма вследствие подавления им механизмов клеточного иммунитета и способности ингибировать апоптоз малигнизированных клеток. Напротив, повышение экспрессии интерлейкина-24, обладающего проапоптотической активностью и стимулирующего дифференцировку клеток, может способствовать повышению эффективности механизмов противоопухолевой резистентности организма. Устранение дисбаланса продукции и/или содержания указанных цитокинов в сыворотке крови может создать условия повышения эффективности терапии пациентов с В-клеточным хроническим лимфолейкозом. Aim. To study serum levels of immunosuppressive cytokines (interleukin (IL)-10 and IL-24) in patients with B-cell chronic lymphocytic leukemia for assessment of the disease progression and elaboration of a new treatment strategy. Methods. 120 patients with B-cell chronic lymphocytic leukemia were enrolled in the study and divided into four groups according to the disease stage (Rai stage I-IV). Control group included 30 healthy volunteers. Concentrations of IL-10 and IL-24 were measured in serum using the enzyme-linked immunosorbent assay (ELISA). Results. Serum levels of IL-10 and IL-24 levels were significantly increased in all patient groups compared to the control. No difference in the cytokines levels between the patient groups was observed. Conclusion. In patients with B-cell chronic lymphocytic leukemia, the increased serum level of IL-10 might impair the antitumor defence by inhibiting the cell immune response and preventing apoptosis of malignant lymphocytes. On the other hand, the increased serum level of IL-24 might oppose these effects by promoting cellular differentiation and inducing apoptosis in malignant cells. Therefore, correction of IL-10/IL-24 imbalance may be a beneficial therapeutic strategy for patients with B-cell chronic lymphocytic leukemia.

scholarly journals Poor Correlation between Pneumococcal IgG and IgM Titers and Opsonophagocytic Activity in Vaccinated Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia

2016 ◽  
Vol 23 (4) ◽  
pp. 379-385 ◽  
Author(s):  
Johanna Karlsson ◽  
Lucy Roalfe ◽  
Harriet Hogevik ◽  
Marta Zancolli ◽  
Björn Andréasson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Elderly Subjects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Waldenström’S Macroglobulinemia ◽  
Control Subjects ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

ABSTRACTPatients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n= 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r= −0.18 to 0.21) or in the group with Waldenstrom's macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r= 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom's macroglobulinemia patients.

Lactate dehydrogenase and its isoenzymes in serum from patients with multiple myeloma.

1989 ◽  
Vol 35 (9) ◽  
pp. 1968-1970 ◽  
Author(s):  
S Copur ◽  
S Kus ◽  
A Kars ◽  
N Renda ◽  
G Tekuzman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Clinical Status ◽  
Control Group ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
The Mean ◽  
Isoenzyme Patterns

Abstract Concentrations of total lactate dehydrogenase (LDH; EC 1.1.1.27) and LDH isoenzyme patterns were studied in serum of 19 patients with multiple myeloma and in 19 healthy controls. Patients were divided into three groups (pretreatment, nonresponders, and responders to treatment), based on their clinical status at the time of blood sampling for LDH. The LDH values were found to be significantly higher (P less than 0.05) in the pretreatment group and in the nonresponders than in the responders and the control group, the mean +/- SE values being 445 +/- 35 and 532 +/- 75 units/mL vs 349 +/- 75 and 190 +/- 7.1 units/mL, respectively. Compared with responders and healthy controls, newly diagnosed patients and nonresponders had slight diminutions in LDH-1 and LDH-2, but increased LDH-3. We conclude that determination of LDH and its isoenzymes in serum can be of value as prognostic factors in patients with multiple myeloma.

scholarly journals Angiogenesis-Related Cytokines, RANKL, and Osteoprotegerin in Multiple Myeloma Patients in relation to Clinical Features and Response to Treatment

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
K. Sfiridaki ◽  
C. A. Pappa ◽  
G. Tsirakis ◽  
P. Kanellou ◽  
M. Kaparou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Serum Levels ◽  
Response To Treatment ◽  
Disease Stage ◽  
Vascular Endothelial ◽  
Newly Diagnosed ◽  
Plateau Phase ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth

An essential cytokine system for the osteoclast biology in multiple myeloma (MM) consists of the receptor of activator of NF-κB ligand (RANKL), its receptor (RANK), and the soluble decoy receptor, osteoprotegerin (OPG). Myeloma cells cause imbalance in OPG/RANKL interactions. We measured serum levels of OPG, soluble (s) RANKL, sRANKL/OPG ratio, markers of disease activity [LDH, CRP, interleukin-6 (IL-6),β2-microglobulin (B2M)], and angiogenic factors [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], in 54 newly diagnosed MM patients and in 25 of them in plateau phase. All the above values were higher in MM patients compared to controls and decreased in plateau phase. sRANKL and RANKL/OPG were higher with advancing disease stage and skeletal grade. Significant correlations were found among RANKL and RANKL/OPG with HGF, LDH, VEGF, IL-6, and B2M. In conclusion, RANKL and OPG play significant roles in MM pathophysiology, as regulators of bone turnover and mediators of angiogenesis.

scholarly journals Plasma Concentrations of Matrilysins MMP-7 and MMP-26 as Diagnostic Biomarkers in Breast Cancer

2021 ◽  
Vol 10 (7) ◽  
pp. 1436
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasma Levels ◽  
Proteolytic Enzymes ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Diagnostic Utility ◽  
Study Results ◽  
Advanced Stages ◽  
Disease Study

Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.

Kinetics of Thrombin Generation in Patients with Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3535-3535 ◽  
Author(s):  
Anna D. Petropoulou ◽  
Grigoris T. Gerotziafas ◽  
Kostas Zervas ◽  
A. Mpanti ◽  
Michel Meyer Samama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Endothelial Cell ◽  
Plasma Levels ◽  
Thrombin Generation ◽  
Cell Damage ◽  
Control Group ◽  
Endothelial Cell Damage ◽  
Thrombotic Risk ◽  
Soluble Thrombomodulin ◽  
Significant Difference

Abstract Thalidomide has emerged as a promising treatment for multiple myeloma (MM). Thrombosis is the most serious complication of thalidomide therapy, essentially when it is combined with dexamethasone. The pathogenesis of thrombosis in MM patients (pts) treated with thalidomide is not clear and probably of multi factorial origin. We used the Thrombin Generation test (TGT) and measured the plasma levels of soluble thrombomodulin (sTM) to better clarify the MM-related and thalidomide-related thrombogenicity. TGT was performed in citrated frozen platelet poor plasma (PPP). Blood was obtained from 26 MM pts, Salmon and Durie stage II and III, 62.5 years old (42–77), 9 males and 17 females, 10 treated with thalidomide (100–200mg/d orally) and dexamethasone (40mg/d for 4 days) (TD group) and 16 receiving no treatment (MM group). 13 healthy volunteers formed the control group. Thrombin Generation (TG) was initiated by adding the PPP reagent (Thrombogram-Thrombinoscope®) and the triggering solution (CaCl2 and fluorogenic substrate). We analyzed the endogenous thrombin potential (ETP), the Cmax and the velocity index of TG. The plasma levels of sTM in PPP were measured by a specific ELISA (Diagnostica Stago, France). In the MM group we observed an increase of the ETP, though not significant compared to the controls. The Cmax was almost equal to the control group value, while the velocity index of TG was statistically lower in the MM group compared to controls. In the TD group, a statistically significant increase of ETP was observed as compared to the control group. The Cmax was higher, compared to controls, though not significantly, whereas the velocity index of TG was almost equal to the control group value. There was no significant difference in the TG parameters between MM and TD groups. sTM in the control group was 45±14ng/ml. Both groups of pts had significantly increased sTM plasma levels as compared to the control but the difference between the two groups did not reach significance. Results are shown in Table 1. In patients with MM coexists an increase of sTM, a marker of endothelial cell damage, together with an increased TG capacity. The addition of thalidomide treatment is associated with a slight but not significant increase of ETP and Cmax. The co-existence of endothelial cell damage with increased TG capacity could be associated to the increased thrombotic risk in MM patients treated with thalidomide. This hypothesis will be controlled in a prospective study. Table 1: Thrombogram parameters and sTM plasma levels of studied pts. Control MM group TD group * Results significantly different between the MM and TD groups and the control group (p<0.05 vs the control group) ETP (nM×min) 1399±297 1651±478 1747±448* Cmax (nM) 366±54 342±52 402±99 Velocity Index (nM/min) 198±45 160±19* 184±65 STM (ng/ml) 45±14 84±42* 73±30*

Treatment of Patients with Multiple Myeloma Complicated by Renal Failure with Bortezomib - Based Regimens.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2739-2739 ◽  
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Erasmia Psimenou ◽  
Irini Grapsa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Median Time ◽  
Objective Response ◽  
Elevated Serum ◽  
Management Problem ◽  
Newly Diagnosed ◽  
Kinetics Of

Abstract Introduction: Renal failure is a common feature of multiple myeloma and a major management problem. There is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents, such as bortezomib, when administered to newly diagnosed or relapsed/refractory patients with renal failure. The purpose of our analysis was to assess the frequency of renal failure improvement and kinetics of serum creatinine in patients who received bortezomib-based regimens. Patients and methods: We evaluated 20 consecutive patients with newly diagnosed (n=7) or relapsed/refractory (n=13) multiple myeloma and renal failure, defined as a serum creatinine ≥ 2mg/dl. Patients’ median age was 66 years (range 43–88 years). Median serum creatinine was 3.8 mg/dl (range 2–11.9 mg/dl) and median creatinine clearance was 15.3 ml/min (range 6.4–33.3). Other features included hemoglobin <10gr/dl in 12 patients, platelets <100 × 109/l in 3 patients and elevated serum LDH in 9 patients. All patients received bortezomib plus dexamethasone alone or in combination with other agents, such as thalidomide, doxorubicin or melphalan. Reversibility of renal failure was defined as a sustained decrease of serum creatinine to <1.5 mg/dl and renal response was defined as ≥50% decrease of serum creatinine from its peak value. Results: Reversal of renal failure was documented in 35% of all patients and the median time to reversal was 23 days. Moreover, 9 patients (45%) had 50% decrease in serum creatinine and the median time to decrease was 34 days. Some decrease of creatinine was documented in 88% of patients. Among four patients who were on renal dialysis, 2 became independent of this procedure after the second and the third cycle of treatment. The objective response rate was 61% and the median progression free survival for responders was 12 months. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Grade 3–4 neutropenia and thrombocytopenia were seen in 28% and 22% of patients respectively. One patient died of infection and bortezomib had to be discontinued in 4 patients due to grade III neurotoxicity. Conclusions: When bortezomib-based regimens are administered to myeloma patients with renal impairment their toxicity and efficacy are similar to those observed in patients with normal renal function. Moreover, these regimens are associated with rapid improvement of renal function in most patients and with reversal of renal failure in one-third of them.

Sign in / Sign up

Export Citation Format

Share Document