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Published in: International Journal of Hematology 6/2013

01-06-2013 | Original Article

Bisphosphonate treatment and renal function in 201 myeloma patients undergoing stem cell transplantation

Authors: S. Schmitt, T. Hielscher, C. Baldus, K. Neben, G. Egerer, J. Hillengaß, M. Raab, D. Hose, A. D. Ho, R. Bergner, H. Goldschmidt, T. M. Moehler

Published in: International Journal of Hematology | Issue 6/2013

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Abstract

Administration of bisphosphonates (BPs) is an essential supportive treatment for reducing bone-related complications in cancer. Deterioration of renal function is one possible side effect of BPs as well as a clinical feature in multiple myeloma. It has been suggested that the nephrotoxicity of different BPs may differ. We performed a retrospective evaluation of renal function in 201 myeloma patients undergoing myeloablative chemotherapy and treatment with ibandronate (I), pamidronate (P), or zoledronate (Z) for up to 36 months. There was no significant deterioration in mean creatinine clearance (CreaCl) in the entire cohort. The percentage of patients experiencing a decrease in CreaCl ≥ 25 % from baseline was 33.0 % in the I group, 44.4 % in the P group and 21.4 % in the Z group, respectively. CreaCl at baseline (P < 0.0001), relapse/progression (P = 0.0019), proteinuria at baseline (P = 0.039), age (P = 0.0031) were identified as significant independent predictors of decrease in renal function. In both descriptive multivariant analyses, we found no evidence of an advantage of any particular BP with respect to effects on renal function. In line with these data, in a subgroup of 90 patients with a baseline CreaCl <90 ml/min, no significant difference was evident between the cohorts of patients treated with different BPs. Regular treatment with the BPs I, P and Z in myeloma patients undergoing intensive chemotherapy appear to be equally safe for up to 3 years in terms of nephrotoxicity.
Literature
1.
go back to reference Ludwig H, Zojer N. Supportive care in multiple myeloma. Best Pract Res Clin Haematol. 2007;20(4):817–35.PubMedCrossRef Ludwig H, Zojer N. Supportive care in multiple myeloma. Best Pract Res Clin Haematol. 2007;20(4):817–35.PubMedCrossRef
2.
go back to reference Terpos E, Sezer O, Croucher PI, Garcia-Sanz R, Boccadoro M, San MJ, Ashcroft J, Blade J, Cavo M, Delforge M, Dimopoulos MA, Facon T, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European myeloma network. Ann Oncol. 2009;20:1303–17.PubMedCrossRef Terpos E, Sezer O, Croucher PI, Garcia-Sanz R, Boccadoro M, San MJ, Ashcroft J, Blade J, Cavo M, Delforge M, Dimopoulos MA, Facon T, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European myeloma network. Ann Oncol. 2009;20:1303–17.PubMedCrossRef
3.
go back to reference Berenson JR, Yellin O, Boccia RV, Flam M, Wong SF, Batuman O, Moezi MM, Woytowitz D, Duvivier H, Nassir Y, Swift RA. Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss. Clin Cancer Res. 2008;14(19):6289–95.PubMedCrossRef Berenson JR, Yellin O, Boccia RV, Flam M, Wong SF, Batuman O, Moezi MM, Woytowitz D, Duvivier H, Nassir Y, Swift RA. Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss. Clin Cancer Res. 2008;14(19):6289–95.PubMedCrossRef
4.
go back to reference Baulch-Brown C, Molloy TJ, Yeh SL, Ma D, Spencer A. Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. Leuk Res. 2007;31(3):341–52.PubMedCrossRef Baulch-Brown C, Molloy TJ, Yeh SL, Ma D, Spencer A. Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. Leuk Res. 2007;31(3):341–52.PubMedCrossRef
5.
go back to reference Kondo H, Mori A. Anti-tumor activity of pamidronate in human multiple myeloma. Leuk Lymphoma. 2002;43(4):919–21.PubMedCrossRef Kondo H, Mori A. Anti-tumor activity of pamidronate in human multiple myeloma. Leuk Lymphoma. 2002;43(4):919–21.PubMedCrossRef
6.
go back to reference Body JJ. The risk of cumulative renal effects of intravenous bisphosphonates. Support Cancer Ther. 2006;3(2):77–83.PubMedCrossRef Body JJ. The risk of cumulative renal effects of intravenous bisphosphonates. Support Cancer Ther. 2006;3(2):77–83.PubMedCrossRef
8.
go back to reference Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D. Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity. Am J Kidney Dis. 2003;41(5):E18.PubMed Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D. Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity. Am J Kidney Dis. 2003;41(5):E18.PubMed
9.
go back to reference Bonomi M, Nortilli R, Molino A, Sava T, Santo A, Caldara A, Cetto GL. Renal toxicity and osteonecrosis of the jaw in cancer patients treated with bisphosphonates: a long-term retrospective analysis. Med Oncol. 2010;27:224–9.PubMedCrossRef Bonomi M, Nortilli R, Molino A, Sava T, Santo A, Caldara A, Cetto GL. Renal toxicity and osteonecrosis of the jaw in cancer patients treated with bisphosphonates: a long-term retrospective analysis. Med Oncol. 2010;27:224–9.PubMedCrossRef
10.
go back to reference Henrich DM, Hoffmann M, Uppenkamp M, Bergner R. Tolerability of dose escalation of ibandronate in patients with multiple myeloma and end-stage renal disease: a case series. Onkologie. 2009;32(8–9):482–6.PubMedCrossRef Henrich DM, Hoffmann M, Uppenkamp M, Bergner R. Tolerability of dose escalation of ibandronate in patients with multiple myeloma and end-stage renal disease: a case series. Onkologie. 2009;32(8–9):482–6.PubMedCrossRef
11.
go back to reference Prakash J, Mandal AK, Vohra R, Wani IA, Hota JK, Raja R, Singh U. Renal disease is a prodrome of multiple myeloma: an analysis of 50 patients from eastern India. Ren Fail. 2009;31(4):267–71.PubMedCrossRef Prakash J, Mandal AK, Vohra R, Wani IA, Hota JK, Raja R, Singh U. Renal disease is a prodrome of multiple myeloma: an analysis of 50 patients from eastern India. Ren Fail. 2009;31(4):267–71.PubMedCrossRef
12.
go back to reference Sengul S, Li M, Batuman V. Myeloma kidney: toward its prevention—with new insights from in vitro and in vivo models of renal injury. J Nephrol. 2009;22(1):17–28.PubMed Sengul S, Li M, Batuman V. Myeloma kidney: toward its prevention—with new insights from in vitro and in vivo models of renal injury. J Nephrol. 2009;22(1):17–28.PubMed
13.
go back to reference Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omede P, Baldi I, Bringhen S, Massaia M, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356(11):1110–20.PubMedCrossRef Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omede P, Baldi I, Bringhen S, Massaia M, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356(11):1110–20.PubMedCrossRef
14.
go back to reference Pinheiro J, Bates D. Linear mixed effect models. Springer; 2009. Pinheiro J, Bates D. Linear mixed effect models. Springer; 2009.
15.
go back to reference R Development Core Team. A language and environment for statistical computing. R Foundation for Statistical Computing 2010. R Development Core Team. A language and environment for statistical computing. R Foundation for Statistical Computing 2010.
16.
go back to reference Diel IJ, Weide R, Koppler H, Antras L, Smith M, Green J, Wintfeld N, Neary M, Duh MS. Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review. Support Care Cancer. 2009;17(6):719–25.PubMedCrossRef Diel IJ, Weide R, Koppler H, Antras L, Smith M, Green J, Wintfeld N, Neary M, Duh MS. Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review. Support Care Cancer. 2009;17(6):719–25.PubMedCrossRef
17.
go back to reference Shah SR, Jean GW, Keisner SV, Ussery SM, Dowell JE. Risk of renal failure in cancer patients with bone metastasis treated with renally adjusted zoledronic acid. Support Care Cancer. 2012;20(1):87–93.PubMedCrossRef Shah SR, Jean GW, Keisner SV, Ussery SM, Dowell JE. Risk of renal failure in cancer patients with bone metastasis treated with renally adjusted zoledronic acid. Support Care Cancer. 2012;20(1):87–93.PubMedCrossRef
18.
go back to reference Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010;376:1989–99.PubMedCrossRef Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010;376:1989–99.PubMedCrossRef
19.
go back to reference Menssen HD, Sakalova A, Fontana A, Herrmann Z, Boewer C, Facon T, et al. Effects of longterm intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. J Clin Oncol. 2002;20:2353–9.PubMedCrossRef Menssen HD, Sakalova A, Fontana A, Herrmann Z, Boewer C, Facon T, et al. Effects of longterm intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. J Clin Oncol. 2002;20:2353–9.PubMedCrossRef
Metadata
Title
Bisphosphonate treatment and renal function in 201 myeloma patients undergoing stem cell transplantation
Authors
S. Schmitt
T. Hielscher
C. Baldus
K. Neben
G. Egerer
J. Hillengaß
M. Raab
D. Hose
A. D. Ho
R. Bergner
H. Goldschmidt
T. M. Moehler
Publication date
01-06-2013
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 6/2013
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-013-1320-1

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