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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 2  |  Page : 335-340
Outcome of patients with multiple myeloma and renal failure on novel regimens


1 Nephrology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Hematologic and Oncologic Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Date of Web Publication11-Mar-2016
 

   Abstract 

Renal involvement occurs in 20-40% of newly diagnosed multiple myeloma (MM) patients, and diagnosis of myeloma is frequently made after investigation for unexplained renal disease. This is a retrospective study between 2006 and 2013 in which 57 consecutive patients seen at the Nephrology Unit with diagnosis of MM were enrolled. MM was diagnosed for the first time because of renal dysfunction and/or proteinuria in these patients. The mean age of the patients (65% male) was 58.3 ± 12.7 years. The median baseline serum creatinine was 3.5 mg/dL (1.4-14.5). Anemia (hemoglobin <12 g/dL) was noted in 88% and hypercalcemia (calcium >10.5 mg/dL) in 35% of patients. Early hemodialysis was started in 28 patients (49%). Thalidomide plus dexamethasone (16% on bortezomib) were the main therapeutic regimens. Three patients (5%) underwent autologous stem cell transplantation. Twenty-six patients (45.6%) died during a median follow-up of 25 months (1-90). The mean age of patients who died was significantly higher than the age in patients who were alive (62.2 ± 12.7 vs. 55.2 ± 11.9 years, respectively; P = 0.037). Early hemodialysis had no significant effect on mortality rate. The one-, threeand fiveyear patient survival was 71%, 54%, and 41%, respectively. The median overall survival of patients was 50 months. Prolonged patient survival can be expected in myeloma patients with renal failure or on dialysis by applying novel therapeutic agents.

How to cite this article:
Soleymanian T, Soleimani A, Musavi A, Mojtahedi K, Hamid G. Outcome of patients with multiple myeloma and renal failure on novel regimens. Saudi J Kidney Dis Transpl 2016;27:335-40

How to cite this URL:
Soleymanian T, Soleimani A, Musavi A, Mojtahedi K, Hamid G. Outcome of patients with multiple myeloma and renal failure on novel regimens. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Jul 21];27:335-40. Available from: http://www.sjkdt.org/text.asp?2016/27/2/335/178557

   Introduction Top


Multiple myeloma (MM) is a plasma cell dyscrasia with an annual incidence of 4.3 per 100,000 population. [1] Renal insufficiency occurs in up to 50% of newly diagnosed patients. [2],[3],[4],[5],[6] Renal involvement in MM typically presents as proteinuria and renal insufficiency and diagnosis of myeloma is frequently made by the investigation of unexplained renal disease. [7] Renal function usually improves after treatment for predisposing factors such as volume depletion, hyperuricemia, hypercalcemia, contrast nephropathy, and cessation of nonsteroidal anti-inflammatory drugs. [8]

MM is the most common malignancy leading to end-stage renal disease (ESRD) and considered for renal replacement therapy (RRT). [8],[9] In recent years, the usage of RRT for myeloma patients has increased, and it is mostly due to improvement in chemotherapy regimens and establishment of autologous stem cell transplantation (ASCT) that lead to prolongation of patient survival permitting better outcome. With the use of novel agents, the outcome of myeloma patients with renal insufficiency and dialysis has increasingly improved. [10]

This study was carried out to identify the characteristics of myeloma patients with renal involvement and also to estimate the outcome of myeloma patients with renal insufficiency or on dialysis.


   Methods Top


We retrospectively enrolled 57 myeloma patients in our Nephrology Unit between 2006 and 2013, in whom MM was diagnosed for the first time while investigating for the cause of renal involvement (renal dysfunction and/or proteinuria). Diagnosis of MM was based on histologic, serologic, and radiographic features and included bone marrow with abnormal plasma cells or histologic confirmation of a plasmacytoma; a monoclonal gammopathy in the serum or urine (except for nonsecretory myeloma); and end-organ damage confirmed by anemia, hypercalcemia, lytic bone lesions, or renal insufficiency. Demographic data, mode of presentation, radiologic assessment, need for dialysis, baseline serum creatinine, urinalysis, 24-h urine protein, hemoglobin, and serum calcium were recorded. Patients were followed-up for their treatment and outcome for a median of 25 months (range: 1-90). Informed consent was obtained from all participants.


   Statistical Analysis Top


Numerical data are presented as mean ± standard deviation or median (range) based on normality of distribution. Variables were compared between groups by Student's t-test and Mann-Whitney U test for continuous variables, and with the Pearson Chi-square for categorical variables. Kaplan-Meier analysis was used to estimate patient survival. Cox regression analysis was applied to determine the independent predictors of survival. Analyses were carried out with SPSS version 16. Significant level was considered as P <0.05.


   Results Top


The mean age of the study patients was 58.3 ± 12.7 years (35-80) and 65% were male. At presentation, the median serum creatinine was 3.5 mg/dL (1.4-14.5), mean hemoglobin was 9.1 ± 1.8 g/dL (5-13), serum calcium was 10.3 ± 1.9 mg/dL (6.4-14.7), and median urine protein was 1455 mg/24-h (50-9500) [Table 1]. Anemia (hemoglobin <12 g/dL) was noted in 88% and hypercalcemia (calcium >10.5 mg/ dL) in 35% of patients. About 57% of patients had proteinuria in the range of 500-3500 mg/ day and 29% had more than 3500 mg/d. Eightysix percent of the patients presented with serum creatinine higher than 2 mg/dL. Weakness (48%), weight loss (36%), and bone pain (72%) were common constitutional features. Radiological bone involvement was noted in 79% of the patients including lytic lesions in 48.5%, vertebral involvement (osteoporosis, pathologic or compression fractures) in 27.5%, and hip fracture in 3% of the patients. In three patients, diagnosis of myeloma was made by kidney biopsy (chronic tubulointerstitial nephritis in two patients and amyloidosis in one). Early hemodialysis was started in 28 patients (49%). Nine patients (16%) received Bortezomib(Velcade) based regimen, and others were mainly on Td (thalidomide plus dexamethasone). Three patients (5%) underwent ASCT. One patient received both ASCT and kidney transplantation. Twenty-six patients (45.6%) died during a median follow-up of 25 months (1-90). The mean age of patients in the group that died was significantly higher than the group that was alive (62.2 ± 12.7 vs. 55.2 ± 11.9 years, P = 0.037, respectively). Early hemodialysis had no significant effect on mortality rate [Table 2]. The one-, threeand five-year patient survival was 71% [standard error (SE): 0.06], 54% (SE: 0.07) and 41% (SE: 0.08), respectively [Figure 1]. The median overall survival of patients was 50 months. On Cox regression analysis, only age had a significant independent effect on patient survival (P = 0.024). The percent of deaths and mean survival (months) during follow-up for ages ≤40, 41-50, 51-60, 61-70, and >70 years were, respectively, 20% and 61 ± 12.3, 36% and 52.3 ± 9.7, 38% and 48.8 ± 7.1, 60% and 37.4 ± 8.2, and 73% and 28.2 ± 7.5 months.
Figure 1: Cumulative patient survival in 57 myeloma patients.

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Table 1: Characteristics of 57 myeloma patients with renal involvement.

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Table 2: Comparison of patients' characteristics between live and dead groups.

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   Discussion Top


In this study, we tried to identify the characteristics of myeloma patients with renal involvement and also to ascertain patient outcome. Surprisingly, our patients were mainly young or in the middle age such that 9% of the patients were younger than 40 years (35-40) and 23% in the range of 41-50 years. In other reports, MM was mostly a disease of older adults with a median age at diagnosis of 66 years and only two and 10% of patients were younger than 40 and 50 years, respectively. [5],[11] The median age at diagnosis in our patients was 59 years.

The frequency of men was higher than women (1.85:1) which is higher than the average in other studies (1.4:1). The prevalence of anemia (88%) and hypercalcemia (35%) was high, while the average in other reports is 73% and 28%, respectively. [5] It was expected because patients presented with renal insufficiency (serum creatinine ≥1.4 mg/dL), in which anemia is a common complication and also hypercalcemia is a common etiology of renal failure in MM.

Kidney pathology in myeloma patients comprises cast nephropathy (40-63%), light-chain deposition disease (19-26%), amyloidosis (7- 30%), and cryoglobulinemic renal disease (<1%). [12],[13] Up to 65% of patients with cast nephropathy develop ESRD soon after diagnosis despite intensive treatment. [12],[13] Patients with severe nephropathy at presentation are most likely to need dialysis therapy and have a little recovery of renal function. [14] By treatment of myeloma patients with dexamethasone and novel agents (thalidomide, lenalidomide, bortezomib), the rate of at least partial recovery of renal function can reach up to 80% depending on the severity of failure. Furthermore, up to 80% of patients who need dialysis therapy at the beginning became independent from dialysis. [15] In previous reports, this rate of recovery was as low as 15%. [14]

The outcome of patients with myeloma depends not only upon the biologic characteristics of plasma cells but also patient-specific features such as performance status, age, and co-morbidities. [5] In the past, the median survival on dialysis was between four and eight months with survival rates of 29-84% at one-year and 19-50% at two-years. [16] The prognosis in patients on dialysis, aside from patient's age and co-morbidities are determined by the stage of myeloma and response to chemotherapy. Patients who respond to chemotherapy seem to have the best prognosis with a mean survival of 47 months versus 17 months in nonresponders. [17] The mortality rate of myeloma patients who need dialysis during the first two months from diagnosis is high and can reach up to 30%. [18] In the European renal association European dialysis and transplantation association registry study, [10] 25% of myeloma patients died within 90 days from the start of RRT; severity of myeloma was the cause of death in one-third of them. In our patients on dialysis, 7% died during the first two months of replacement therapy (36% during first six months).

It has been shown that renal failure most likely does not affect the response to chemotherapy, which is in a range of 40-60%. [17],[18],[19],[20] Nevertheless, renal dysfunction may increase the probability of infections, difficulties in fluid management, dose adjustment of drugs, and tolerability of chemotherapy. [2],[3],[4],[21]

Most studies indicate that serum creatinine at presentation is only predictive of worse renal outcome, and patient survival on dialysis was similar to those who did not need dialysis therapy. [22] These studies suggest that replacement therapy has no harmful effect on patient survival. Nowadays, the median overall survival of myeloma patients on dialysis is reportedly 36-60 months, and could be much longer with novel treatments. [23],[24]

The relative good prognosis in this study is presumed to be because of the use of novel agents and more importantly, the younger age of the patients. It was shown that older patients, due to higher co-morbidities and lowperformance status, have limitation to tolerate chemotherapy and therefore, will have a poor outcome in spite of having myeloma with properties often associated with a better prognosis. [25],[26] In agreement with other reports, we found that age is an independent predictor of patient outcome and patients older than 50 years had significantly shorter survival.

The long-term survival of myeloma patients justifies the implementation of kidney transplantation as a therapeutic option in steady young patients who are in complete remission for more than one year. [27],[28],[29] The successful use of ASCT in dialysis-dependent myeloma patients may aid renal transplantation in these patients. In this study, the patients received mostly Td and 16% received bortezomib-based therapy. Three patients underwent ASCT, of whom one also received kidney transplantation.

Unfortunately, in this study, staging data for severity of MM was not accessible in all patients. Therefore, we could not evaluate the impact of disease severity on patient outcome. However, we believe that our study provided useful information (characteristics and outcome) on myeloma patients with renal insufficiency treated by novel agents.

In conclusion, myeloma patients with renal insufficiency dependent on dialysis or not, can benefit from novel therapeutic agents and even ASCT to have a prolonged survival with or without a kidney transplant.

Conflict of interest: None declared.

 
   References Top

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Tsakiris DJ, Stel VS, Finne P, et al. Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA registry study. Nephrol Dial Transplant 2010;25:1200-6.  Back to cited text no. 10
    
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Ganeval D, Rabian C, Guérin V, Pertuiset N, Landais P, Jungers P. Treatment of multiple myeloma with renal involvement. Adv Nephrol Necker Hosp 1992;21:347-70.  Back to cited text no. 12
    
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Kastritis E, Anagnostopoulos A, Roussou M, et al. Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents. Haematologica 2007;92:546-9.  Back to cited text no. 15
    
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[PUBMED]    

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Correspondence Address:
Tayebeh Soleymanian
Nephrology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran
Iran
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DOI: 10.4103/1319-2442.178557

PMID: 26997388

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