Management of myeloma-associated renal dysfunction in the era of novel therapies

Gaballa, Mahmoud R.; Laubach, Jacob P.; Schlossman, Robert; Redman, Katherine; Noonan, Kimberly; Mitsiades, Constantine S.; Ghobrial, Irène M.; Munshi, Nikhil C.; Anderson, Kenneth C.; Richardson, Paul G.

doi:10.1586/ehm.11.72

Cited by 30 publications

(39 citation statements)

References 118 publications

(92 reference statements)

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“…Renal function was assessed by estimated glomerular filtration rate (eGFR), calculated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation [17]. The degree of RI, based on values of eGFR measured as mL/min/1.73 m 2 , was graded as follows: G1 (normal renal function) 90; G2 (mild RI) 60-89; G3a (mild to moderate RI) 45-59; G3b (moderate to severe RI) 30-44; G4 (severe RI) 15-29; G5 (renal failure) <15 or on dialysis. Renal response was defined as complete (CR renal ), partial (PR renal ), or minor (MR renal ), according to the criteria formulated by the IMWG.…”

Section: Methodsmentioning

confidence: 99%

Bortezomib‐based therapy combined with high cut‐off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment

et al. 2015

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Multiple myeloma (MM) is often associated with renal insufficiency (RI) which adversely influences the prognosis. Several studies demonstrated that bortezomib can improve both renal function and outcome. We prospectively evaluated 21 newly diagnosed MM patients with severe renal impairment secondary to tubularinterstitial damage, most of them due to myeloma kidney, who were primarily treated with bortezomib-based therapy combined with high cut-off hemodialysis (HCOD). The median serum creatinine level at baseline was 6.44 mg dL 21 and calculated median estimated glomerular filtration rate (eGFR), according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was 8 mL/min/1.73 m 2 . Serum free light chain (sFLC) median concentration was 6,040 mg L 21. Post induction and best stringent complete response rates were 19 and 38%, respectively. Responses were fast, occurring within a median of 1.4 months. The combination of bortezomib and HCOD led to a prompt and remarkable (>90%) decrease in sFLC levels. Sixteen patients (76%) became dialysis independent within a median of 32 days. With a median follow up of 17.2 months, the 3-year PFS and OS were 76 and 67%, respectively. No early deaths were observed. This study demonstrates that incorporation of bortezomib into induction therapy combined with HCOD is a highly effective strategy in rescuing renal function and improving outcomes in patients with MM and RI.

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Section: Methodsmentioning

confidence: 99%

Bortezomib‐based therapy combined with high cut‐off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment

et al. 2015

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“…Bortezomib is a proteasome inhibitor that was found to be particularly effective in treatment of the plasma cell dyscrasia multiple myeloma and indicated by the FDA for the treatment of advanced myeloma in 2003 (45). Subsequent studies showed a benefit in myeloma with renal involvement and antibody-mediated rejection of kidney allografts by targeting antibody-producing plasma cells (46,47). Side effects of peripheral neuropathy, cytopenias, and gastrointestinal effects occur in a dose-dependent fashion.…”

Section: Plasma Cell Targeting: Bortezomibmentioning

confidence: 99%

Immunosuppressive Medications

Wiseman¹

2016

Clinical Journal of the American Society of Nephrology

202

165

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Immunosuppressive agents are commonly used in the nephrologist's practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist.

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“…Although thalidomide pharmacokinetics, like bortezomib pharmacokinetics, are relatively unaffected by renal dysfunction, hyperkalemia has been reported (79,80). Thalidomide can be used at doses of typically 50-100 mg daily as tolerated, with encouraging activity combined with other agents (81). For example, high-dose dexamethasone regimens combined with lenalidomide or thalidomide act rapidly and have beneficial effects on paraprotein-mediated renal impairment similar to the effects of bortezomib-based regimens, while helping to preserve stem cell transplantation options (82,83).…”

Section: Systemic Therapymentioning

confidence: 99%

Kidney Disease and Multiple Myeloma

Heher

Rennke

Laubach

et al. 2013

Clinical Journal of the American Society of Nephrology

144

122

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SummaryKidney injury is a common complication of multiple myeloma and other plasma cell dyscrasias, and it is associated with increased mortality. Multiple pathogenic mechanisms can contribute to kidney injury in the patient with myeloma, some of which are the result of nephrotoxic monoclonal Ig and some of which are independent of paraprotein deposition. The pathogenic mechanisms that underlie paraprotein-related kidney disease are increasingly well understood. A novel assay allowing the quantification of free light chains in the serum has aided the diagnosis of new onset disease and allowed for the earlier detection of relapse. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes. Stem cell transplantation remains a mainstay of management for younger patients with myeloma who are suitable candidates for intensive therapy, whereas the role of new drugs, plasma exchange, and kidney transplantation continues to evolve.

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Management of myeloma-associated renal dysfunction in the era of novel therapies

Cited by 30 publications

References 118 publications

Bortezomib‐based therapy combined with high cut‐off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment

Bortezomib‐based therapy combined with high cut‐off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment

Immunosuppressive Medications

Kidney Disease and Multiple Myeloma

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