The International Scoring System (ISS) for Multiple Myeloma Remains a Robust Prognostic Tool Independently of Patients' Renal Function

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3036-3036
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Marie-Christine Kyrtsonis ◽  
John Meletis ◽  
Eurydiki Michalis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Renal Dysfunction ◽  
Median Survival ◽  
Staging System ◽  
Tumor Burden ◽  
Prognostic Performance ◽  
Stage 4 ◽  
Stage 1

Abstract Abstract 3036 The ISS introduced by Greipp et al (J Clin Oncol 2005) represents today the most widely used staging system for patients with multiple myeloma (MM) because it is based on two readily available variables: serum albumin and beta2-microglobulin. Serum beta2-microglobulin not only reflects myeloma tumor load but it is also increased in patients with renal dysfunction. Thus, there have been concerns that ISS-3 stage may include MM patients with renal impairment in whom elevated beta2-microglobulin does not reflect tumor burden but rather the degree of renal dysfunction. To address this issue, we assessed the impact of patients' renal function on the prognostic performance of ISS. Our analysis included data from 1516 patients with symptomatic MM that had been entered into the database of the Greek Myeloma Study Group. Renal function was assessed by the estimated GFR (eGFR), which was calculated using the modified MDRD formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American) and the degree of renal dysfunction was staged according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) classification of chronic kidney disease (CKD) as follows: stage 1 eGFR ≥90 ml/min; stage 2 eGFR of 60–89 ml/min; stage 3 eGFR of 30–59 ml/min; stage 4 eGFR of 15–29 ml/min and stage 5 eGFR <15 ml/min or under dialysis. At the time of treatment initiation, 788 patients had stage 1 or 2 CKD and 728 patients had stage 3–5 CKD. According to ISS, 29% patients had ISS-1, 38% patients had ISS-2 and 33% ISS-3. Renal impairment was significantly more common in ISS-3 patients: 76% of ISS-3 patients had stage 3–5 CKD compared to 42% and 27% for ISS-2 and ISS-1, respectively (p<0.001). Similarly, the incidence of stage 4 or 5 CKD was higher in ISS-3 (23% and 20%, respectively) than in patients with ISS-2 (6% and 1.5%, respectively) or ISS-1 (4% and 1%, p<0.001). In the univariate analysis, which included all patients, stage 3–5 CKD was associated with inferior survival (31 months vs. 51 months for those with stage 1 or 2 CKD, p<0.001). However, CKD stages had not an independent prognostic value in the multivariate analysis. Subsequently, we analyzed the prognostic significance of renal function in each ISS group separately. ISS-1 patients with stage 1 or 2 CKD had a median survival of 76 months vs. 56 months for patients with stage 3–5 CKD (p=0.053). In ISS-2, the respective median survival was 49 months and 29 months for stage 1–2 CKD vs. stage 3–5 CKD (p=0.02). In contrast, in patients with ISS-3 the median survival was similar (30 vs. 24 months, p=0.292) for patients with stage 1–2 CKD and stage 3–5 CKD. Multivariate analysis performed in each ISS subgroup revealed that renal function (either as a dichotomous or as a continuous variable) was not an independent prognostic factor in any of ISS stages: HR=1.031, p=0.873 for ISS-1; HR=0.996, p=0.123 for ISS-2 and HR=1.09, p=0.6 for ISS-3. We conclude that ISS is a simple, yet powerful prognostic staging system. The robustness of ISS remains unaffected by the degree of renal function. In patients with ISS-3, which includes many patients with renal dysfunction, elevated beta2-microglobulin reflects tumor burden, despite its increase due to renal impairment. Our data in a large population of myeloma patients indicate that adjustment for renal function will not improve the prognostic performance across all ISS stages. Disclosures: No relevant conflicts of interest to declare.

Renal Impairment Is Not An Independent Adverse Prognostic Factor In Multiple Myeloma Patients Who Are Treated Upfront with Novel Agent-Based Regimens

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3033-3033 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Renal Disease ◽  
Renal Dysfunction ◽  
Prognostic Impact ◽  
Agent Based ◽  
Stage 1 ◽  
Novel Agent

Abstract Abstract 3033 The adverse prognosis of renal impairment in patients with multiple myeloma (MM) has been reported in several series. However, the prognostic impact of renal dysfunction on the survival of MM patients who are treated upfront with novel agents has not been clearly defined. To address this question we studied 180 consecutive patients who received upfront novel agent (thalidomide, bortezomib or lenalidomide)-based regimens, in a single center in Athens, Greece. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. Renal function, estimated by the glomelural filtration rate (eGFR) was assessed using the simplified Modification of Diet in Renal Disease (MDRD) formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American). Patients were divided into 5 groups according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) classification. According to this classification, stage 1 includes patients with eGFR ≥90 ml/min, while stage 2 includes patients with eGFR between 60–89 ml/min, stage 3 with eGFR between 30–59 ml/min, stage 4 with eGFR between 15–29 ml/min and stage 5 includes patients with eGFR below 15 ml/min or patients who undergo dialysis. Eighty-five patients (47%) had stage 3–5 CKD and 95 (53%) had stage 1 or 2 CKD. One half of our patients (51%) were 70 years of age or older. Advanced age (p=0.001), anemia (p<0.001), low serum albumin (p=0.017), hypercalcemia (p<0.001), elevated beta2-microglobulin (p<0.001) and Bence Jones proteinuria >2 g/day (p<0.001) were associated with stage 3–5 CKD. The majority of patients with International Scoring System (ISS)-3 myeloma had advanced renal disease (stage 3–5 CKD in 76%) in comparison with ISS-2 (33%) or ISS-1 (10.5%) patients (p<0.001). Eighty-one percent of our patients received upfront an IMiD-based therapy, while 19% received bortezomib-based regimens. The dose of lenalidomide was adjusted according to renal function. The frequency of advanced CKD was similar among patients treated with IMiDs- or bortezomib-based regimens (47% vs. 48.5%, p=0.843). Response to primary treatment was similar between patients with stage 3–5 CKD and patients with stage 1 or 2 CKD (72.6% vs. 78.7%, respectively; p=0.343). In the univariate analysis, variables associated with worse survival were: stage 3–5 CKD (median survival 39 months vs. not reached in stage 1 or 2 CKD; p=0.001), age ≥70 years (p<0.001), anemia (p=0.005), hypercalcemia (p=0.012), ISS stage (p<0.001) and LDH ≥300 IU/L (p=0.007). However, in the multivariate analysis, the presence of renal dysfunction (stage 3–5 CKD) or the degree of renal dysfunction (evaluating each CKD stage separately) was not independently associated with survival. Age >70 years (p<0.001), corrected serum calcium ≥11.5 mg/dl (p=0.04) and elevated LDH ≥300 IU/L (p=0.001) were the only independent factors associated with worse survival. The same results were obtained when we assessed renal function as a continuous variable. We also evaluated the effect of CKD staging on the survival of patients within each ISS stage and we did not find any statistically significant correlation. We conclude that the presence °r the degree of renal dysfunction has no independent prognostic impact on the survival of multiple myeloma patients who are treated upfront with novel agent-based regimens. Disclosures: No relevant conflicts of interest to declare.

Renal Impairment and the Use of Bisphosphonates in Patients with Multiple Myeloma: Retrospective Analysis of 114 Patients with Respect to Age and Other Clinical Characteristics.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4918-4918
Author(s):  
Sam Mazj ◽  
Stuart M. Lichtman
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Renal Dysfunction ◽  
Renal Toxicity ◽  
Clinical Course ◽  
The Elderly ◽  
Close Monitoring ◽  
Renal Function Deterioration ◽  
The Impact

Abstract Backgound: The clinical course of multiple myeloma is often associated with significant bone related morbidity. This can be modified by the use of bisphosphonates. Studies have shown renal toxicity associated with different bisphosphonates especially following the exposure of zoledronic acid. Published literature suggests renal function deterioration occurs in 8.8–15.2% of patients at recommended dose of 4 mg infused intravenously over 15 minutes. Methods: We retrospectively reviewed the records of all patients with multiple myeloma who received bisphosphonates during the period of January 2002-June 2004 at our institution. 114 patients were analyzed (male/female 63/51; age-median 69;mean 71;range 40–92). 61 (54%) were >70 years of age. They received a total of 1301 doses (mean 11.4) during this period. The type of bisphosphonate used was: zolendronate: 58; pamidronate: 23; pamidronate changed to zolendronate (both) : 33. Patients were categorized to the type and sequence of bisphosphonates [ pamidronate vs. zoledronate and pamidronate followed by zoledronate (both) ], age and sex. Renal dysfunction was defined as an increase in serum creatinine of >0.5 mg/dl over baseline. Results: There were 19 patients (16.7%) who developed renal dysfunction. 15 of the 19 episodes (79%) occurred in the 70 years and older group. The table shows the distribution of patients, type of bisphosphonate and the distribution of patients with renal toxicity. Conclusion: This analysis showed increase in renal dysfunction occurs in all ages with use of bisphosphonates. The elderly may be particularly susceptible to this toxicity. Although we have not analyzed the impact of associated comorbidities (including type of multiple myeloma) leading to renal insufficiency in this study, the elderly patients may need more close monitoring of renal function with the use of bisphosphonates. Age and renal impairment with bisphosphonate use Age Zolendronate Pamidronate Both Total Number in paranthesis indicates the renal impairment case 40–49 6 (0) 2 (0) 2 (0) 10 (0) 50–59 10 (0) 1 (0) 4 (0) 15 (0) 60–69 14 (2) 3 (0) 11 (1) 28(3) 70–79 19 (3) 9 (1) 14 (4) 42 (8) 80+ 9 (3) 8 (0) 2 (4) 19 (7) Total 58 (9) 23 (1) 33 (9) 114 (19)

An Analysis of Occurrence and Prognosis Related Factors of Renal Dysfunction in Patients with Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4732-4732
Author(s):  
Rong Fu ◽  
Ting Wang ◽  
Zonghong Shao
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Tumor Burden ◽  
Protection Factor ◽  
Related Factors ◽  
Factors Associated ◽  
Renal Function Recovery ◽  
Function Recovery

Abstract Objective To analysis the occurrence and prognosis related factors in renal dysfunction with multiple myeloma(MM). Methods Seventy-four cases with MM were enrolled in this study. The risk factors of occurrence and prognosis were analyzed. Results The incidence of renal dysfunction (RD) with MM was 56.8%, Age, hypertention, hemoglobin, serum ALB and GLO levels, serum β2MG, serum calcium and phosphonium level, the percentage of myeloma cells in bone marrow, types of MM, Durie-Salmon stage were the single factors associated with the incidence of RD with MM. Hypertention, serum β2MG and ALB levels were the multiple factors associated with the incidence of RD with MM. ALB was the protection factor and the other two were risk factors. The renal function recovered rapidly in the patients who received CR or received blood transfusion. The patients with renal dysfunction survived shorter (28±5months) than those with normal renal function (42±6months). Renal dysfunction caused more MM patients death(84.6%) in 3 months. Conclusion Hypertention and high tumor burden were the risk factors of renal dysfunction in MM, effective chemothemapy and support treatment help renal function recovery.

Validation Of Criteria For Renal Response In Patients With Multiple Myeloma (MM) Who Present With Severe Renal Dysfunction

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3176-3176
Author(s):  
Meletios A. Dimopoulos ◽  
Evangelos Terpos ◽  
Maria Roussou ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Median Survival ◽  
Early Death ◽  
Response Criteria ◽  
High Dose ◽  
Primary Therapy ◽  
Renal Response ◽  
Stage 4 ◽  
Mdrd Formula

Abstract Severe renal impairment (RI) in MM patients is a medical emergency. Immediate antimyeloma therapy and appropriate supportive measures are needed because these patients are at high risk for early death and other complications associated with their renal dysfunction. Antimyeloma therapy may improve renal function in a significant proportion of patients and the choice of treatment may also be guided by the degree of RI. For the evaluation of the recovery of renal function IMWG has proposed specific criteria (Dimopoulos et al, JCO 2010), which are based on changes of calculated GFR. A new formula for the estimation of GFR has been used by nephrologists as a more accurate method of renal function assessment (CKD-EPI formula). In order to evaluate the currently available IMWG criteria, by using the new CKD-EPI formula, we assessed renal response in patients with newly diagnosed MM who presented with severe RI. We also evaluated simplified criteria for renal response and compared patient outcomes with the IMWG criteria. We analyzed the outcomes of 105 consecutive patients who presented with severe RI (eGFR <30 ml/min/1.73m2) from 1995 to 2012. GFR was calculated using two different equations: the MDRD and the CKD-EPI. Per IMWG criteria, renal response was defined as complete (CRrenal, when GFR ≥60 ml/min), partial response (PRrenal, when GFR from <15 ml/min to 30-59 ml/min), or minor (MRrenal, with GFR increase either from <15 ml/min to 15-29 ml/min or from 15-29 ml/min to 30-59 ml/min). We also applied simplified criteria in which patients who presented with stage 5 RI (eGFR<15 ml/min or on dialysis) should double their eGFR and improve to at least stage 4 RI (eGFR 15-29 ml/min) or become independent of dialysis and patients with stage 4, increase their eGFR by at least 50% and improve to at least stage 3 (eGFR 30-59 ml/min). Most patients (68%) were >65 years of age; 36% were >75 years, while 92% had ISS-3 disease. Primary therapy with bortezomib-based regimens was given in 38% of patients, 43% received IMiD-based therapy (34% thalidomide- and 9% lenalidomide-based) and 19% high dose dexamethasone and conventional chemotherapy (CC) regimens. When GFR was calculated by the MDRD formula then 51% had stage 4 and 49% had stage 5 RI, while by the CKD-EPI formula, 49% had stage 4 and 51% stage 5 RI. Thus, RI stage change between stage 4 & 5 occurred in only 2% of patients with the use of CKD-EPI vs. MDRD equation. According to the IMWG criteria, with GFR calculated by the MDRD formula, 36 (34%) patients achieved CRrenal, 8 (7.5%) PRrenal and 33 (31%) MRrenal. When GFR was calculated by the CKD-EPI formula, then 35 (33%) patients achieved a CRrenal, 8 (7.5%) PRrenal and 34 (32%) MRrenal; only in 3 patients (3%) there was a discrepancy in the quality of renal response between the two equations. Major renal response (CR+PRrenal) was more frequent with bortezomib (57.5% vs. 34% for IMiDs vs. 26% for high dose Dexa+CC, p=0.034). When we applied the proposed simplified renal response criteria, then 47 (45%) patients were considered responders; responses were more frequent in patients treated with bortezomib (62.5% vs. 35% for IMiDs vs. 32% for high dose Dexa+CC, p=0.016). The median survival for all patients who presented with severe RI was 31 months (95% CI 16-46). Early death (<2 months from initiation of therapy) occurred in 15 (14%) patients; in only 3% of patients ≤65 years vs. 20% of patients >65 years (p=0.022). The median survival of patients who presented with stage 4 vs. stage 5 RI was similar (31 vs. 38 months, p=0.230). For patients who survived at least 2 months, the median survival of the patients who achieved ≥PRrenal was 53 months (by MDRD and CKD-EPI) vs. 43 months for patients who had minor renal response vs. 42 months for patients who did not have a renal response, by the IMWG criteria. Among patients who survived at least 2 months, median survival of the responders according to the proposed simplified renal response criteria was 53 vs. 44 of the non responders (p=0.3). There was no difference in the performance of either criteria for overall survival, risk of death at 6 or 12 months, with either of the formulas for eGFR calculation. We conclude that in unselected MM patients with severe RI, the criteria for the improvement of renal function can be simplified without any significant change in their prognostic significance. The GFR calculated by the CKD-EPI can also be used for the assessment of renal response in patients with MM. Disclosures: No relevant conflicts of interest to declare.

Macrofocal Multple Myeloma Is a Particular Subgroup of Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1855-1855 ◽  
Author(s):  
Jianling Fan ◽  
Jian Hou ◽  
Juan Du ◽  
Lina Jin ◽  
Lihui Peng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Staging System ◽  
Tumor Burden ◽  
Bone Lesions ◽  
Serum Free Light Chain ◽  
Secretory Type ◽  
Stage 1

Abstract Some young multiple myeloma (MM) patients, coined macrofocal MM, have been reported to present with multiple lytic bone lesions and less than 10% bone marrow plasma cells (BMPCs). They usually have low tumor burden and favorable outcome. To further understand the clinical and laboratory features of macrofocal MM, we retrospectively analyzed about 1000 symptomatic MM patients of two centers and found that 49 (4.9%) patients fulfilled the criteria of macrofocal MM. Median age was 54 years; 39 (80%) were male. The immunoglobulin subtype included IgG (13), IgA (5), IgD (4), light chain only (4) and non-secretory type (23). International Staging System (ISS) stage 1 in 45 (92%), and no stage 3 patient. Durie-Salmon (DS) Staging System stage 3A in 48 (98%), and 2A in 1. Extramedullary plasmacytomas (EMPs) in 39 (80%) patients. The mean percentage of BMPCs was 2.1%, and 44 (90%) patients had less than 5% BMPCs. No patients had hypercalcemia and renal impairment. FISH cytogenetics, available in 11 patients, showed IgH translocation in 7, 13q del in 2, t(4;14) in 1, 1q21 amp in 6 and p53 del in 2 patients. Serum free light chain (sFLC), available in 14 patients, showed abnormal sFLC in 7 of 14 patients and 4 in 7 non-secretory type patients. Thirty eight (77.6%) patients received new drug-based induction therapies and 14 patients received autologous stem cell transplantation (ASCT) as consolidation therapy. After a median follow-up of 36 months,the estimated median progression-free survival (PFS) was 41 months and the median overall survival time (OS) had not been reached. Forty four macrofocal MM with ISS stage 1 and DS stage 3A were compared to all (93) typical symptomatic MM patients who were diagnosed at the same period with the same stages according to both ISS and DS Staging System. For macrofocal MM, there were significantly more male patients and EMPs, higher hemoglobin levels and lowerb2-microglobulin (b2M) levels than that of typical MM. There were no significant differences in the proportions of patients received novel agents-based chemotherapy and ASCT between two groups, however, the estimated median PFS of macrofocal MM was significant superior to typical MM (41 vs 23 months, respectively; P= 0.001) (Figure 1), and the estimated median OS was also better in macrofocal MM than typical MM (not reached vs 61 months; P= 0.004) (Figure 2). Multivariate analysis showed that only the type of disease was the independent prognostic factor of both PFS and OS. In summary, Macrofocal MM is a particular subgroup of MM with multiple bone lesions and lower tumor burden, higher frequency of EMPs, and better survival than typical symptomatic MM. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Fan: The National Natural Science Foundation of China: Research Funding. Hou:Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Haematologica ◽  
2021 ◽  
Author(s):  
Marcelo Capra ◽  
Thomas Martin ◽  
Philippe Moreau ◽  
Ross Baker ◽  
Ludek Pour ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Subgroup Analysis ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Phase 3 ◽  
New Therapies

Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The Phase 3 IKEMA study (NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) vs Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group

2010 ◽  
Vol 28 (33) ◽  
pp. 4976-4984 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Evangelos Terpos ◽  
Asher Chanan-Khan ◽  
Nelson Leung ◽  
Heinz Ludwig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Light Chain ◽  
Renal Injury ◽  
High Dose ◽  
Acute Renal Injury ◽  
High Dose Dexamethasone ◽  
Cast Nephropathy ◽  
High Dose Melphalan

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

Creatinine Clearance Is More Important Prognostic Factor Than ß2 Microglobulin in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4864-4864
Author(s):  
Jae-Pil Yun ◽  
Cheolwon Suh ◽  
Eunkyoung Lee ◽  
Jai Won Chang ◽  
Won Seok Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Creatinine Clearance ◽  
Survival Time ◽  
Univariate Analysis ◽  
Staging System ◽  
Rank Test ◽  
Significant Prognostic Factor ◽  
Important Prognostic Factor ◽  
Stage 1

Abstract In the new staging system of multiple myeloma (MM) by South West Oncology Group (SWOG), the concentration of serum β2 microglobulin (β2m) and serum albumin were focused as the most important prognostic factors for survival. However, serum concentration of β2m has been known as an indicator of glomerular filtration rate. The aim of this study was to compare the prognostic value of the level of β2m with that of creatinine clearance (Ccr) in patients with multiple myeloma. Retrospectively, from January 1, 1996 to November 30, 2003, we reviewed 176 MM patients (M: F 110:66 mean age: 58.5±11.0) whose 24-hour urinary creatinine clearance was available at the time of diagnosis. We collected clinical data such as hemoglobin, serum creatinine, calcium, albumin, β2m, creatinine clearance before chemotherapies, and patients’ survival time. Pretreatment β2m was inversely related to Ccr (Spearman’s correlation coefficient = −0.781, P <0.01). In univariate analysis, relative risk (RR) of death was 1.047 (p< 0.001) for β2m and 0.985 (p< 0.001) for Ccr. But multivariate analysis using Cox’s proportional hazard model showed β2m was not significant prognostic factor in patients’ survival after adjustment for Ccr (RR 1.025, p=0.054) but Ccr was an independent risk factor of death after adjustment for β2m (RR 0.990, p=0.013). And univariate analysis identified that RR for β2m is not significant in 88 MM patients (66 patients with β2m ≥ 2.5mg/l) with relatively normal renal function (Ccr ≥ 50 ml/min) (RR = 1.110, p=0.306) We could propose another new staging system with β2m replaced by Ccr in SWOG staging system. The stages were defined as: stage 1, Ccr ≥ 80ml/min; stage 2, 50< Ccr <80; stage 3, Ccr < 50 and albumin ≥ 3.0g/dl; and stage 4 Ccr < 50 ml/min and albumin< 3.0 g/dl. According to this proposed staging system, median survival time of each stage from 1 to 4 is 1475, 887, 513, and 196 days, respectively. (Log Rank test < 0.0001) In conclusion, Ccr could be more important prognostic factor than the level of β2m in patients of MM and we propose that Ccr should be reassessed as the component of staging system of MM.

The Epidemic of Chronic Kidney Disease in Patients Referred to a Hematologist for Anemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5521-5521
Author(s):  
Brian Zimmer ◽  
Dana Wentzel ◽  
James Reed ◽  
Sherrine Eid ◽  
Eliot Friedman ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
General Population ◽  
Serum Creatinine ◽  
Strong Association ◽  
Chart Audit ◽  
Stage 4 ◽  
The Mean ◽  
Stage 1

Abstract NHANES survey estimates the prevalence of CKD to be approximately 11% in the general population and 25% in the population over 65 years of age, and the prevalence of Chronic Kidney Disease (CKD) associated anemia approaches 75% in Stage 5 CKD. Despite the high prevalence of CKD, and its strong association with anemia, many patients diagnosed with anemia and referred to a hematologist for evaluation frequently have the diagnosis of CKD overlooked, especially if one is using a serum creatinine to assess renal function. A more accurate method of assessing renal function and to appropriately stage CKD is the use of an estimated glomerular filtration rate (eGFR) utilizing the modified MDRD equation. With the realization that CKD clearly has become known as a significant magnifier of cardiovascular risk (CVR), the importance of making the diagnosis of CKD has become quite apparent. Hypothesis: Patients referred to a hematologist for evaluation of anemia represent a population enriched with CKD. A retrospective chart audit was performed on patients being referred to a hematology practice from community physicians for the evaluation of anemia from January 2004 through December 31, 2005. All patients with a prior knowledge of CKD and a history of malignancy or myelodysplastic process were excluded from the study. The cohort consisted of 256 patients (37.5 % male and 62.5 % female) with a mean age of 67.56 ± 15.9 years. The mean serum creatinine was 1.16 ± .74 mg/dL with a mean calculated GFR by the modified MDRD (4 variable) equation of 69.9 ± 34.2 ml/min/1.73 m2. The mean ± SEM serum creatinine by stage of CKD in our patient population is: Stage 1: 0.67 ± 0.14 mg/dL, Stage 2: 0.92 ± 0.15 mg/dL, Stage 3: 1.40 ± 0.29 mg/dL, Stage 4: 2.23 ± 0.53 mg/dL, and Stage 5: 5.2 ± 2.89 mg/dL. Conservatively, we defined CKD as GFR <60 as urinalysis, imaging, or biopsy data were not available. In conclusion, an astounding 42.2 % of patients referred to a hematologist for the evaluation of anemia have CKD as compared to an estimated prevalence of 11 % in the general population reported by K/DOQI. Not only were these patients not aware of their diagnosis of CKD, but, of note also is the fact that 5.1 % were not aware of the presence of advanced CKD (GFR < 30) and 4 patients had Stage 5 CKD without awareness. 55.8 % of the patients over the age of 65 with anemia have CKD as compared to an estimated 25 % of the general population over the age of 65. This information stresses the need to assess all anemia patients for CKD and to appropriately stage them. Given the well accepted association between CKD and CVR, physicians caring for these patients can then stress the need for aggressive pursuit of both traditional and non traditional risk factor reduction to circumvent the significant CVR that is present in this population. Prevalence of Abnormal Renal Function by GFR Frequency Percent *K/DOQI = National Kidney Foundation’s Kidney Disease Outcome Quality Initiative GFR > 90 (Normal /K/DOQI* Stage 1) 51 19.9 GFR 89 - 60 (K/DOQI Stage 2) 97 37.9 GFR 59 - 30 (K/DOQI Stage 3) 95 37.1 GFR 29 - 15 (K/DOQI Stage 4) 9 3.5 GFR < 15 (K/DOQI Stage 5) 4 1.6

Novel Agents Overcome the Adverse Prognosis Imparted by Compromised Renal Function in Patients with Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2726-2726 ◽  
Author(s):  
Mehul Patel ◽  
Taimur Sher ◽  
Sikander Ailawadhi ◽  
Terry Mashtare ◽  
Wei Tan ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Serum Creatinine ◽  
Median Survival ◽  
Impaired Renal Function ◽  
Pegylated Liposomal Doxorubicin ◽  
Novel Agents ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier

Abstract INTRODUCTION: Impaired renal function in patients with multiple myeloma (MM) is associated with adverse clinical outcome. Historically, the renal status is reported as serum creatinine (SCr) only. Introduction of novel agents (thalidomide, lenalidomide, bortezomib and pegylated liposomal doxorubicin) in MM therapeutics has improved clinical responses and overall survival. An important question that remains largely unanswered is if these agents deliver equal benefit to patients with impaired renal function. Thus we investigate the overall benefit of novel agents in MM patients with renal impairment. METHODS: All MM patients treated between January 2000 and December 2007 at Roswell Park Cancer Institute (RPCI) where included in this analysis. Extent of disease was assessed based on the Durie-Salmon staging system. We determined glomerular filtration rate (GFR) to asses renal function more accurately. GFR was calculated utilizing the Modification of Diet in Renal Disease (MDRD) equation. Patient cohorts were defined based on severity of renal impairment per the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKD-KDOQI) guidelines based on the GFR value into normal &gt;90, mild 60–89, moderate 30–59, severe 15–29 and kidney failure &lt;15 ml/min/1.73m^2. Because there were only few patients in the last two groups (GFR of 15–29 =11 and GFR &lt;15 =13), they were combined into a single cohort of severe renal impairment (GFR &lt;30=24). We also defined patient cohorts based on a previously reported classification in MM wherein patients were divided based on severity of renal impairment into normal &gt;80, mild 50–80, moderate 30–49 and severe &lt;30 ml/min/1.73m^2. Survival curves and median survival were calculated by Kaplan-Meier method. Survival differences were calculated using a log-rank test. A 0.05 nominal significance level was used in all statistical testing. RESULTS: A total of 175 patients (M=88, F=87) with a median age 60 years (range 34–88) were evaluated. Majority of patients had stage III disease (64%), 57.1% had IgG myeloma and lytic bone disease present in 67.4% of the patients. Median values for SCr, serum calcium, blood urea nitrogen, serum albumin and hemoglobin were 1.1mg/dl (range-0.5–10.3), 9.5 mg/dl (range-7.5- 7.2), 18 mg/dl (range-5–107), 4.0 g/dl (range-2.2–5.5) and 11.5 g/dl (range-6.8–17.1) respectively. SCr &gt;2 mg/dl was seen in only 16% patients and 41.1% patients had GFR in the range of 60–89 ml/min/1.73m^2. Patients received an average of 2 treatments. Use of at least one of the novel agent was seen in 86.3% patients (Immunomodulatory drugs =130, Bortezomib = 97, Pegylated liposomal doxorubicin =65). Median survival for patients with SCr &lt;2.0 and SCr&gt;2.0 was 67.4 months (45.4 – 92.7 months) and 38.4 months (15.3 months – not reached) respectively. Median survival for patients with normal GFR and mild, moderate and severe renal impairment based on the NKD-KDOQI guidelines was 76.1 months (37.5 months – not reached), 55.32 months (34.8 months – not reached), 67.4 months (45.4 months – not reached) and 24.9 months (15.3 months – not reached) respectively. Median survival for patient cohorts defined based on a previously reported classification in MM was similar to that seen with the NKD-KDOQI classification. We noted no significant survival advantage of normal renal function over renally impaired patients (Figure 1 & 2) despite evaluations based either by using the traditional approach of SCr (p=0.15; log rank test) or by more sensitive renal function assessment by GFR (p=0.21; log rank test). CONCLUSIONS: We conclude that in MM patients the previously reported and commonly perceived adverse prognosis imparted by impaired renal function can no longer be validated and that routine incorporation of novel agents has overcome this adverse prognosis. These findings are consistent with the impact of novel agents reported in context with MM with aggressive molecular profiles. Figure 1: Kaplan-Meier curve for survival by serum creatinine (SCr) Figure 1:. Kaplan-Meier curve for survival by serum creatinine (SCr)

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