Managing renal complications in multiple myeloma

Citation:

Fotiou D, Dimopoulos MA, Kastritis E. Managing renal complications in multiple myeloma. Expert Review of Hematology [Internet]. 2016;9(9):839 - 850.

Abstract:

Introduction: About 20–40% of patients with multiple myeloma (MM) will present with some degree of renal impairment (RI) and about 25% of patients will experience RI at later disease stages. Patients with MM and RI have poorer overall survival and are at higher risk of early death. Areas covered: The mechanisms of acute renal damage in MM are covered and the issues around diagnosis and renal evaluation response are discussed. The importance of optimal supportive care is stressed and the role and effectiveness of different anti-myeloma agents covered including the role of high cut-off hemodialysis, autologous stem cell transplantation and kidney transplant. Expert commentary: Outcomes of patients with RI and rates of renal recovery have improved with the use of novel anti-myeloma agents. Bortezomib-dexamethasone backbone regimes (±third agent) are the current first choice in newly diagnosed patients. In relapsed/refractory disease additional treatment options include newer novel agents. © 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. e101819; Hutchison, C.A., Cockwell, 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 (2012) 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; 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, pp. 1544-1557; 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; 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. e538-E548; Inker, L.A., Schmid, C.H., Tighiouart, H., Estimating glomerular filtration rate from serum creatinine and cystatin C (2012) N Engl J Med, 367 (1), pp. 20-29; 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; Kleber, M., Ihorst, G., Deschler, B., Detection of renal impairment as one specific comorbidity factor in multiple myeloma: multicenter study in 198 consecutive patients (2009) Eur J Haematol, 83 (6), pp. 519-527; Kleber, M., Ihorst, G., Udi, J., Prognostic risk factor evaluation in patients with relapsed or refractory multiple myeloma receiving lenalidomide treatment: analysis of renal function by eGFR and of additional comorbidities by comorbidity appraisal (2012) Clin Lymphoma Myeloma Leuk, 12 (1), pp. 38-48; Kleber, M., Ihorst, G., Gross, B., Validation of the Freiburg Comorbidity Index in 466 multiple myeloma patients and combination with the international staging system are highly predictive for outcome (2013) Clin Lymphoma Myeloma Leuk, 13 (5), pp. 541-551; 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; 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. e296; 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; Cobb, J., Plantinga, L., Luthi, J.-C., Pre-ESRD care and mortality in incident ESRD patients with multiple myeloma (2016) Am J Clin Oncol; MRC Working Party on Leukaemia in Adults. Analysis and management of renal failure in fourth MRC myelomatosis trial (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.-I., 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; 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; 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; 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; 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, pp. 499-502; 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; 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; Dimopoulos, M.A., Christoulas, D., Roussou, M., Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment (2010) Eur J Haematol, 85 (1), pp. 1-5; 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; 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; 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; 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; 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; Siegel, D.S., Baz, R.P., Chen, M., 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; Berdeja, J., Jagannath, 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; 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, pp. 1551-1560; Scheid, C., Sonneveld, P., Schmidt-Wolf, I.G.H., 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; 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; 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; Vij, R.R.P., Siegel, D.S., Hofmeister, C.C., 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), 13; Weisel, K.C., Moreau, D.M., Lacy, M., 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), 31; 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 (Meet Abstr), 124 (abstract 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., 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, 96, pp. 564-577; 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; 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; Lonial, S., Dimopoulos, M., Palumbo, A., Elotuzumab therapy for relapsed or refractory multiple myeloma (2015) N Engl J Med, 373 (7), pp. 621-631; Yan, X., Clemens, P.L., 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; 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.M., 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); Gupta, N., Hanley, M.J., Harvey, D., (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; 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., García-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; 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; 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; 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; 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

Website