Early Mortality After Diagnosis of Multiple Myeloma: Analysis of Patients Entered Onto the United Kingdom Medical Research Council Trials Between 1980 and 2002—Medical Research Council Adult Leukaemia Working Party

Augustson, Bradley; Begum, Gulnaz; Dunn, Janet A.; Barth, Nicola J.; Davies, Faith E.; Morgan, Gareth J.; Behrens, Judith; Smith, Alastair G.; Child, J. A.; Drayson, Mark T.

doi:10.1200/jco.2005.03.2086

Cited by 435 publications

(396 citation statements)

References 43 publications

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“…1,38 Patients who present with acute renal failure have increased early mortality, reaching up to 30% within the first two months in some series. 2,37 Furthermore, renal impairment may adversely affect the outcome of myeloma patients in various ways. Drug dosing is often complicated, whereas many potentially nephrotoxic but useful drugs are deferred.…”

Section: The Impact Of Renal Failure In the Prognosis Of Myeloma Patimentioning

confidence: 99%

Pathogenesis and treatment of renal failure in multiple myeloma

et al. 2008

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Renal failure is a frequent complication in patients with multiple myeloma (MM) that causes significant morbidity. In the majority of cases, renal impairment is caused by the accumulation and precipitation of light chains, which form casts in the distal tubules, resulting in renal obstruction. In addition, myeloma light chains are also directly toxic on proximal renal tubules, further adding to renal dysfunction. Adequate hydration, correction of hypercalcemia and hyperuricemia and antimyeloma therapy should be initiated promptly. Recovery of renal function has been reported in a significant proportion of patients treated with conventional chemotherapy, especially when high-dose dexamethasone is also used. Severe renal impairment and large amount of proteinuria are associated with a lower probability of renal recovery. Novel agents, such as thalidomide, bortezomib and lenalidomide, have significant activity in pretreated and untreated MM patients. Although there is limited experience with thalidomide and lenalidomide in patients with renal failure, data suggest that bortezomib may be beneficial in this population. Clinical studies that have included newly diagnosed and refractory patients indicate that bortezomib-based regimens may result in rapid reversal of renal failure in up to 50% of patients and that full doses of bortezomib can be administered without additional toxicity.

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Section: The Impact Of Renal Failure In the Prognosis Of Myeloma Patimentioning

confidence: 99%

Pathogenesis and treatment of renal failure in multiple myeloma

et al. 2008

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“…Defined by abnormal creatinine clearance, renal insufficiency is present in nearly one half of myeloma patients at presentation and associated with increased mortality. The presence of coexistent kidney disease limits therapeutic options and stem cell transplant eligibility (1,2). In some series, survival is reduced to less than 1 year in patients with myeloma-associated AKI who do not recover renal function, and in fact, the reversibility of myeloma-associated renal injury is more predictive of patient survival than the response to systemic chemotherapy (3,4).…”

Section: Introductionmentioning

confidence: 99%

Kidney Disease and Multiple Myeloma

Heher

Rennke

Laubach

et al. 2013

Clinical Journal of the American Society of Nephrology

145

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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“…1 A series of large multicenter trials identified renal insufficiency in almost a third of MM patients who experienced death within 60 days of diagnosis. 2 Moreover, data from the United States Renal Data System revealed a significant difference in the 2-year all-cause mortality in patients with end-stage renal disease when it was due to MM compared with other causes. 3 Treatment options in patients with MM and RI have been limited.…”

Section: Introductionmentioning

confidence: 99%

Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival

Sweiss

Patel

Culos

et al. 2016

Bone Marrow Transplant

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Data on the effectiveness and toxicity of high-dose melphalan in patients with renal impairment (RI) are lacking. We evaluated the impact of RI on outcomes of patients with multiple myeloma treated with melphalan 200 mg/m 2 (Mel200) and autologous stem cell transplantation. Similar baseline characteristics were seen among 46 patients with creatinine clearance (CrCl) o 60 mL/min (median 50 mL/min, range 20-59) and 103 patients with CrCl ⩾ 60 mL/min (median 83 mL/min, range 60-128). Patients with CrCl o60 mL/min had longer time to neutrophil (P = 0.008) and platelet engraftment (P o 0.001). Diarrhea, duration of total parenteral nutrition use and infection were significantly higher in the CrCl o 60 mL/min group. With a median follow-up of 35 months (range 2-132) in the CrCl o60 mL/min group and 47 months (range 1-45) in the CrCl ⩾ 60 mL/min group, overall survival was comparable between the two groups. Median treatment-free survival was longer in the RI group (37 vs 17 months, P = 0.0025). Multivariate analysis showed CrCl o 60 mL/min (hazard ratio (HR) 3.5), and prior proteasome inhibitor therapy (HR 2.441) both predicted longer treatment-free survival. We consider Mel200 safe and effective in patients with CrCl between 30 and 60 mL/min.

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Early Mortality After Diagnosis of Multiple Myeloma: Analysis of Patients Entered Onto the United Kingdom Medical Research Council Trials Between 1980 and 2002—Medical Research Council Adult Leukaemia Working Party

Abstract: A tenth of patients die within 60 days of diagnosis of MM. Infection and renal failure are the main direct causes of early mortality, which cannot be accurately predicted by presenting prognostic features. All patients should be considered at high risk of death during induction therapy.

Cited by 435 publications

References 43 publications

Pathogenesis and treatment of renal failure in multiple myeloma

Pathogenesis and treatment of renal failure in multiple myeloma

Kidney Disease and Multiple Myeloma

Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival

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