Abstract:
Introduction: Renal impairment (RI) is one of the most common complication of multiple myeloma (MM). RI is present in almost 20% of MM patients at diagnosis and in 40%-50% of patients during the course of their disease. Areas covered: Biology along with tools for diagnosis and management of RI are reported in this paper. Papers published in PubMed and reported abstracts up to May 2016 were used. Expert opinion: Moderate and severe RI increases the risk of early death; thus rapid intervention and initiation of anti-myeloma treatment is essential and improves renal outcomes in RI patients. Bortezomib and dexamethasone triplet combinations are the current standard of therapy for MM patients with acute kidney injury due to cast nephropathy; they offer high rates of both anti-myeloma response and renal recovery. Thalidomide and lenalidomide may be used in bortezomib refractory patients. In the relapsed/refractory setting additional treatment options such as carfilzomib, pomalidomide and monoclonal antibodies are available; however, there is limited data for their effects on patients with RI. High dose melphalan with autologous stem cell transplantation should be considered in otherwise eligible patients with RI. Finally, high cut-off hemodialysis membranes do not seem to offer significant additive effects on anti-myeloma therapies. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Notes:
Export Date: 18 February 2017References: Hutchison, C.A., Bladé, J., Cockwell, P., Novel approaches for reducing free light chains in patients with myeloma kidney (2012) Nat Rev Nephrol, 8 (4), pp. 234-243;Leung, N., Nasr, S.H., Myeloma-related kidney disease (2014) Adv Chronic Kidney Dis, 21 (1), pp. 36-47;
Kastritis, E., Terpos, E., Dimopoulos, M.A., Current treatments for renal failure due to multiple myeloma (2013) Expert Opin Pharmacother, 14 (11), pp. 1477-1495;
Haynes, R.J., Read, S., Collins, G.P., Presentation and survival of patients with severe acute kidney injury and multiple myeloma: a 20-year experience from a single centre (2010) Nephrol Dial Transplant, 25 (2), pp. 419-426;
Dimopoulos, M.A., Delimpasi, S., Katodritou, E., Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents (2014) Ann Oncol, 25 (1), pp. 195-200;
Uttervall, K., Duru, A.D., Lund, J., The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment (2014) PLoS One, 9 (7), p. 101819;
Hutchison, C.A., Cockwel, L.P., Stringer, S., Early reduction of serum-free light chains associates with renal recovery in myeloma kidney (2011) J Am Soc Nephrol, 22 (6), pp. 1129-1136;
Nasr, S.H., Valeri, A.M., Sethi, S., Clinicopathologic correlations in multiple myeloma: a case series of 190 patients with kidney biopsies (2012) Am J Kidney Dis, 59 (6), pp. 786-794;
Basnayake, K., Stringer, S.J., Hutchison, C.A., The biology of immunoglobulin free light chains and kidney injury (2011) Kidney Int, 79 (12), pp. 1289-1301;
Ying, W.-Z., Wang, P.-X., Aaron, K.J., Immunoglobulin light chains activate nuclear factor-kappaB in renal epithelial cells through a Src-dependent mechanism (2011) Blood, 117 (4), pp. 1301-1307;
Hutchison, C.A., Batuman, V., Behrens, J., The pathogenesis and diagnosis of acute kidney injury in multiple myeloma (2011) Nat Rev Nephrol, 8 (1), pp. 43-51;
Leung, N., Gertz, M., Kyle, R.A., Urinary albumin excretion patterns of patients with cast nephropathy and other monoclonal gammopathy-related kidney diseases (2012) Clin J Am Soc Nephrol, 7 (12), pp. 1964-1968;
Nasr, S.H., Valeri, A.M., Cornell, L.D., Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution (2012) Clin J Am Soc Nephrol, 7 (2), pp. 231-239;
Terpos, E., Kleber, M., Engelhardt, M., European Myeloma Network guidelines for the management of multiple myeloma-related complications (2015) Haematologica, 100 (10), pp. 1254-1266;
Tosi, P., Tomassetti, S., Merli, A., Serum free light-chain assay for the detection and monitoring of multiple myeloma and related conditions (2013) Ther Adv Hematol, 4 (1), pp. 37-41;
Dimopoulos, M.A., Terpos, E., Chanan-Khan, A., Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group (2010) J Clin Oncol, 28 (33), pp. 4976-4984;
Dimopoulos, M.A., Sonneveld, P., Leung, N., International Myeloma Working Group Recommendations for the diagnosis and management of myeloma-related renal impairment (2016) J Clin Oncol, 34 (13), pp. 1544-1557;
Rajkumar, S.V., Dimopoulos, M.A., Palumbo, A., International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma (2014) Lancet Oncol, 15 (12), pp. 538-548;
Inker, L.A., Schmi, D.C.H., Tighiouart, H., Estimating glomerular filtration rate from serum creatinine and cystatin C (2012) N Engl J Med, 367 (1), pp. 20-29;
Terpos, E., Christoulas, D., Kastritis, E., The Chronic Kidney Disease Epidemiology Collaboration cystatin C (CKD-EPI-CysC) equation has an independent prognostic value for overall survival in newly diagnosed patients with symptomatic multiple myeloma; is it time to change from MDRD to CKD-EPI-CysC equations? (2013) Eur J Haematol, 91 (4), pp. 347-355;
Papassotiriou, G.P., Kastritis, E., Gkotzamanidou, M., Neutrophil gelatinase-associated lipocalin and cystatin C are sensitive markers of renal injury in patients with multiple myeloma (2016) Clin Lymphoma Myeloma Leuk, 16 (1), pp. 29-35;
Ando, M., Mori, J., Ohashi, K., A comparative assessment of the RIFLE, AKIN and conventional criteria for acute kidney injury after hematopoietic SCT (2010) Bone Marrow Transplant, 45 (9), pp. 1427-1434;
Shi, H., Zhang, W., Li, X., Application of RIFLE criteria in patients with multiple myeloma with acute kidney injury: a 15-year retrospective, single center, cohort study (2014) Leuk Lymphoma, 55 (5), pp. 1076-1082;
Eleftherakis-Papapiakovou, E., Kastritis, E., Roussou, M., Renal impairment is not an independent adverse prognostic factor in patients with multiple myeloma treated upfront with novel agent-based regimens (2011) Leuk Lymphoma, 52 (12), pp. 2299-2303;
Mhaskar, R., Redzepovic, J., Wheatley, K., Bisphosphonates in multiple myeloma: a network meta-analysis (2012) Cochrane Database Syst Rev, 5, p. CD003188;
Terpos, E., Morgan, G., Dimopoulos, M.A., International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease (2013) J Clin Oncol, 31 (18), pp. 2347-2357;
Ludwig, H., Adam, Z., Hajek, R., Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study (2010) J Clin Oncol, 28 (30), pp. 4635-4641;
Dimopoulos, M.A., Roussou, M., Gkotzamanidou, M., The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma (2013) Leukemia, 27 (2), pp. 423-429;
Gonsalves, W.I., Leung, N., Rajkumar, S.V., Improvement in renal function and its impact on survival in patients with newly diagnosed multiple myeloma (2015) Blood Cancer J, 5, p. 296;
Dimopoulos, M.A., Roussou, M., Gavriatopoulou, M., Bortezomib-based triplets are associated with a high probability of dialysis independence and rapid renal recovery in newly diagnosed myeloma patients with severe renal failure or those requiring dialysis (2016) Am J Hematol, 91 (5), pp. 499-502;
Tsakiris, D.J., Stel, V.S., Finne, P., 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 (2010) Nephrol Dial Transplant, 25 (4), pp. 1200-1206;
Decourt, A., Gondouin, B., Delaroziere, J.C., Trends in survival and renal recovery in patients with multiple myeloma or light-chain amyloidosis on chronic dialysis (2016) Clin J Am Soc Nephrol, 11 (3), pp. 431-441;
Cobb, J., Plantinga, L., Luthi, J.-C., Pre-ESRD care and mortality in incident ESRD patients with multiple myeloma (2016) Am J Clin Oncol;
Analysis and management of renal failure in fourth MRC myelomatosis trial. MRC working party on leukaemia in adults (1984) Br Med J (Clin Res Ed), 288 (6428), pp. 1411-1416;
Cohen, B., Laish, I., Brosh-Nissimov, T., Efficacy of urine alkalinization by oral administration of sodium bicarbonate: a prospective open-label trial (2013) Am J Emerg Med, 31 (12), pp. 1703-1706;
Matsue, K., Fujiwara, H., Iwama, K., Reversal of dialysis-dependent renal failure in patients with advanced multiple myeloma: single institutional experiences over 8 years (2010) Ann Hematol, 89 (3), pp. 291-297;
Kastritis, E., Anagnostopoulos, A., Roussou, M., Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents (2007) Haematologica, 92 (4), pp. 546-549;
Alexanian, R., Barlogie, B., Dixon, D., Renal failure in multiple myeloma. Pathogenesis and prognostic implications (1990) Arch Intern Med, 150 (8), pp. 1693-1695;
Ramasamy, K., Dimopoulos, M.A., Niels, W., (2015) Safety of treatment (Tx) with pomalidomide (POM) and low-dose dexamethasone (LoDEX) in patients (Pts) with relapsed or refractory multiple myeloma (RRMM) and renal impairment (RI), including those on dialysis, , Blood Abstact 374, ASH, Annual Meeting, Dec;
Burnette, B.L., Leung, N., Rajkumar, S.V., Renal improvement in myeloma with bortezomib plus plasma exchange (2011) N Engl J Med, 364 (24), pp. 2365-2366;
Morabito, F., Gentile, M., Ciolli, S., Safety and efficacy of bortezomib-based regimens for multiple myeloma patients with renal impairment: a retrospective study of Italian Myeloma Network GIMEMA (2010) Eur J Haematol, 84 (3), pp. 223-228;
Morabito, F., Gentile, M., Mazzone, C., Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment (2011) Blood, 118 (22), pp. 5759-5766;
Scheid, C., Sonneveld, P., Schmidt-Wolf, I.G., Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma: a subgroup analysis from the HOVON-65/GMMG-HD4 trial (2014) Haematologica, 99 (1), pp. 148-154;
Harris, E., Behrens, J., Samson, D., Use of thalidomide in patients with myeloma and renal failure may be associated with unexplained hyperkalaemia (2003) Br J Haematol, 122 (1), pp. 160-161;
Fakhouri, F., Guerraoui, H., Presne, C., Thalidomide in patients with multiple myeloma and renal failure (2004) Br J Haematol, 125 (1), pp. 96-97;
Tosi, P., Zamagni, E., Tacchetti, P., Thalidomide-dexamethasone as induction therapy before autologous stem cell transplantation in patients with newly diagnosed multiple myeloma and renal insufficiency (2010) Biol Blood Marrow Transplant, 16 (8), pp. 1115-1121;
Tosi, P., Zamagni, E., Cellini, C., Thalidomide alone or in combination with dexamethasone in patients with advanced, relapsed or refractory multiple myeloma and renal failure (2004) Eur J Haematol, 73 (2), pp. 98-103;
Klein, U., Neben, K., Hielscher, T., Lenalidomide in combination with dexamethasone: effective regimen in patients with relapsed or refractory multiple myeloma complicated by renal impairment (2011) Ann Hematol, 90 (4), pp. 429-439;
Dimopoulos, M., Alegre, A., Stadtmauer, E.A., The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function (2010) Cancer, 116 (16), pp. 3807-3814;
Ludwig, H., Rauch, E., Kuehr, T., Lenalidomide and dexamethasone for acute light chain-induced renal failure: a phase II study (2015) Haematologica, 100 (3), pp. 385-391;
De La Rubia, J., Roig, M., Ibáñez, A., Activity and safety of lenalidomide and dexamethasone in patients with multiple myeloma requiring dialysis: a Spanish multicenter retrospective study (2010) Eur J Haematol, 85 (4), pp. 363-365;
Rajkumar, S.V., Jacobus, S., Callander, N.S., Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial (2010) Lancet Oncol, 11 (1), pp. 29-37;
Hoffmann, M., Kasserra, C., Reyes, J., Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration (2013) Cancer Chemother Pharmacol, 71 (2), pp. 489-501;
Richardson, P.G., Siegel, D.S., Vij, R., Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study (2014) Blood, 123 (12), pp. 1826-1832;
Vij, R., Richardson, P., Siegel, D.S., Pomalidomide plus low-dose dexamethasone (POM+LoDEX) in RRMM: analyses based on prior therapy and renal function (2013) Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr), 13Suppl. 1;
Siegel, D.S., Richardson, P., Baz, R., Pomalidomide (POM) with low-dose dexamethasone (LoDEX) in patients with relapsed and refractory multiple myeloma (RRMM): impact of renal function on patient outcomes (2012) Blood (ASH Annu Meet Abstr), 120;
Weisel, K.C., Dimopoulos, M.A., Moreau, P., Pomalidomide plus low-dose dexamethasone (POM+LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): MM-003 analysis of patients (pts) with moderate renal impairment (RI) (2013) J Clin Oncol (ASCO Annu Meet Proc), 31Suppl;
Weisel, K., Dimopoulos, M.A., Cavo, M., Pomalidomide + low-dose dexamethasone in patients with refractory or relapsed multiple myeloma and renal impairment: analysis of aptients from the phse 3b stratus trial (MM-010) (2014) Blood, 124, p. 4755;
Matous, J., Siegel, D.S., Lonial, S., MM-008: a phase 1 trial evaluating pharmacokinetics and tolerability of Pomalidomide + low-dose dexamethasone in patients with relapsed or refractory and refractory multiple and renal impairment (2014) Blood (Meeting Abstracts), 124, p. 4730;
Sonneveld, P., Heyne, N., Kueenburg, E., MM-013: an ongoing phase 2 trial of pomalidomide and low-dose dexamethasone (POM + LoDEX) in relapsed/refractory multiple myeloma (RRMM) with moderate or severe renal impairment (RI) including patients (pts) undergoing hemodialysis (2014) J Clin Oncol, 32, p. 52;
Dimopoulos, M.A., Sonneveld, P., Siegel, D., Carfilzomib and pomalidomide in patients with relapsed and/or refractory multiple myeloma with baseline risk factors (2015) Ann Oncol, 26 (11), pp. 2247-2256;
Dimopoulos, M.A., Leleu, X., Palumbo, A., Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma (2014) Leukemia, 28 (8), pp. 1573-1585;
Muchtar, E., Gertz, M.A., Magen, H., A practical review on carfilzomib in multiple myeloma (2016) Eur J Haematol;
Badros, A.Z., Vij, R., Martin, T., Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety (2013) Leukemia, 27 (8), pp. 1707-1714;
Siegel, D.S., Martin, T., Wang, M., A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma (2012) Blood, 120 (14), pp. 2817-2825;
Siegel, D., Martin, T., Nooka, A., Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies (2013) Haematologica, 98 (11), pp. 1753-1761;
Harvey, R.D., Incidence and management of adverse events in patients with relapsed and/or refractory multiple myeloma receiving single-agent carfilzomib (2014) Clin Pharmacol, 6, pp. 87-96;
Rosenthal, A., Luthi, J., Belohlavek, M., Carfilzomib and the cardiorenal system in myeloma: an endothelial effect? (2016) Blood Cancer J, 6, p. 384;
Dimopoulos, M.A., Moreau, P., Palumbo, A., Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study (2016) Lancet Oncol, 17 (1), pp. 27-38;
Stewart, A.K., Rajkumar, S.V., Dimopoulos, M.A., Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma (2015) N Engl J Med, 372 (2), pp. 142-152;
Lonial, S., Dimopoulos, M.A., Palumbo, A., Elotuzumab therapy for relapsed or refractory multiple myeloma (2015) N Engl J Med, 373 (7), pp. 621-631;
Berdeja, J., Jannagath, S., Zonder, J., Pharmacokinetics and safety of Elotuzumab combined with Lenalidomide and dexamethasone in patients with multiple myeloma and various levels of renal impairment: results of a Phase Ib Study (2016) Clin Lymphoma Myeloma Leuk, 16 (3), pp. 129-138;
Yan, X., Clemens, P., Puchalski, T., (2015) Target-mediated drug disposition of Daratumumab following intravenous infusion in relapsed or refractory multiple myeloma after prior proteasome inhibitors and immunomodulatory drugs: a population pharmacokinetic analysis, , ASH Oral and Poster Abstracts;
Lonial, S., Weiss, B.M., Usmani, S.Z., Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial (2016) Lancet, 387 (10027), pp. 1551-1556;
Orlowski, R.Z., Novel agents for multiple myeloma to overcome resistance in phase III clinical trials (2013) Semin Oncol, 40 (5), pp. 634-651;
San-Miguel, J.F., Hungria, V.T., Yoon, S.S., Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial (2014) Lancet Oncol, 15 (11), pp. 1195-1206;
Moreau, P., Masszi, T., Grzasko, N., (2015) Ixazomib, an investigational oral proteasome inhibitor (PI), in combination with lenalidomide and dexamethasone (IRd), significantly extends progression-free survival (PFS) for patients (Pts) with relapsed and/or refractory multiple myeloma (RRMM): the phase 3 tourmaline-MM1 study (NCT01564537), , ASH Abstracts;
Gupta, N., Hanley, M.J., Harvey, D.R., (2015) Phase 1/1b pharmacokinetic (PK) and safety study of the investigational oral proteasome inhibitor (PI) ixazomib in relapsed/refractory multiple myeloma (RRMM) patients (Pts) with severe renal impairment or end-stage renal disease (ESRD) requiring hemodialysis, , ASH Annual Meeting Abstract;
Tricot, G., Alberts, D.S., Johnson, C., Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study (1996) Clin Cancer Res, 2 (6), pp. 947-952;
Carlson, K., Melphalan 200 mg/m2 with blood stem cell support as first-line myeloma therapy: impact of glomerular filtration rate on engraftment, transplantation-related toxicity and survival (2005) Bone Marrow Transplant, 35 (10), pp. 985-990;
El Fakih, R., Fox, P., Popat, U., Autologous hematopoietic stem cell transplantation in dialysis-dependent myeloma patients (2015) Clin Lymphoma Myeloma Leuk, 15 (8), pp. 472-476;
Badros, A., Barlogie, B., Siegel, E., Results of autologous stem cell transplant in multiple myeloma patients with renal failure (2001) Br J Haematol, 114 (4), pp. 822-829;
San Miguel, J.F., Lahuerta, J.J., Garcia-Sanz, R., Are myeloma patients with renal failure candidates for autologous stem cell transplantation? (2000) Hematol J, 1 (1), pp. 28-36;
Knudsen, L.M., Nielsen, B., Gimsing, P., Autologous stem cell transplantation in multiple myeloma: outcome in patients with renal failure (2005) Eur J Haematol, 75 (1), pp. 27-33;
Glavey, S.V., Gertz, M.A., Dispenzieri, A., Long-term outcome of patients with multiple [corrected] myeloma-related advanced renal failure following auto-SCT (2013) Bone Marrow Transplant, 48 (12), pp. 1543-1547;
St Bernard, R., Chodirker, L., Masih-Khan, E., Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure (2015) Bone Marrow Transplant, 50 (1), pp. 95-99;
Breitkreutz, I., Heiss, C., Perne, A., Bortezomib improves outcome after SCT in multiple myeloma patients with end-stage renal failure (2014) Bone Marrow Transplant, 49 (11), pp. 1371-1375;
Hutchison, C.A., Heyne, N., Airia, P., Immunoglobulin free light chain levels and recovery from myeloma kidney on treatment with chemotherapy and high cut-off haemodialysis (2012) Nephrol Dial Transplant, 27 (10), pp. 3823-3828;
Hutchison, C.A., Bradwell, A.R., Cook, M., Treatment of acute renal failure secondary to multiple myeloma with chemotherapy and extended high cut-off hemodialysis (2009) Clin J Am Soc Nephrol, 4 (4), pp. 745-754;
Harding, S., Provot, F., Beuscart, J.B., Aggregated serum free light chains may prevent adequate removal by high cut-off haemodialysis (2011) Nephrol Dial Transplant, 26 (4), p. 1438;
Zannetti, B.A., Zamagni, E., Santostefano, M., Bortezomib-based therapy combined with high cut-off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment (2015) Am J Hematol, 90 (7), pp. 647-652;
Nayak, L., Lazarus, H.M., Renal allografts in plasma cell myeloma hematopoietic cell graft recipients: on the verge of an explosion? (2013) Bone Marrow Transplant, 48 (3), pp. 338-345
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