Detection of renal impairment as one specific comorbidity factor in multiple myeloma: multicenter study in 198 consecutive patients
ABSTRACT Comorbidity factors have been reported in cancer patients to predict progression free survival (PFS) and overall survival (OS). Renal impairment (RI) is postulated as one negative prognostic factor in multiple myeloma (MM). The study aim was to detect the best way to define RI and the impact of different RI stages on MM outcome.
In this multicenter analysis, we determined RI [serum creatinine, estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) and Cockcroft-Gault] and other prognostic factors in 198 MM patients to ascertain their value on PFS and OS.
Median serum creatinine was 0.9 mg/dL in all patients, whereas the eGFR - being decreased with a median of 80 mL/min/1.73 m(2)- allowed to detect early stages of RI. Via univariate analysis, we observed increasing hazard ratios (HRs) for impaired OS with deteriorating eGFR: with eGFR(MDRD)<90 and <30, HRs were 1.3 and 2.9, respectively. Multivariate analysis determined RI with eGFR<30 and <50 as well as age >59 yr as most important variables for OS. By incorporating eGFR<30 as the most relevant factor determined via multivariate analysis and beta(2)-microglobulin (beta(2)-MG) in a novel MM-risk score, we identified patients with significantly differing OS: median survival with 0, 1 or 2 risk factors were 71, 48, and 24 months, respectively.
These findings demonstrate that RI is frequent in MM, best detected via eGFR determination and an important prognostic factor. eGFR in combination with beta(2)-MG allows definitive risk stratification with largely differing survival in MM.
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ABSTRACT: Renal impairment is a common complication of multiple myeloma. It is found in about 20-25% of patients at diagnosis and in up to 50% at some point during the disease course. The presence of renal insufficiency diminishes quality of life and is associated with increased mortality, although the outcomes of patients after successful induction therapy are comparable to those with normal renal function. Therefore, the treatment of multiple myeloma patients with renal impairment is a major challenge and should aim to achieve remission in a large proportion of patients. New drugs introduced to the treatment of multiple myeloma over the past decade have an established place in the treatment of patients with renal failure. Bortezomib appears to be most beneficial in this setting and in combination with other drugs gives a chance to obtain rapid remission and related improvement of renal function. Immunomodulatory drugs such as thalidomide and lenalidomide may also be used successfully in patients with renal insufficiency, although for the latter drug appropriate dose adjustments are necessary. The presence of renal failure is not a contraindication to autologous bone marrow transplantation in patients eligible for this procedure. Among the classical cytotoxic agents bendamustine should particularly be considered in patients with renal insufficiency. Appropriate supportive care is also extremely important in the management of myeloma patients with renal failure. It may include plasmapheresis and removal of free light chains with high cut-off hemodialysis, adapted dosage of bisphosphonates, and avoidance of drugs and conditions that may impair renal function.Clinical Lymphoma, Myeloma and Leukemia 10/2014; 15(4). DOI:10.1016/j.clml.2014.09.012 · 1.93 Impact Factor
Article: Multiple Myeloma and Kidney Disease[Show abstract] [Hide abstract]
ABSTRACT: Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis.The Scientific World Journal 10/2013; 2013:487285. DOI:10.1155/2013/487285 · 1.73 Impact Factor
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ABSTRACT: In Canada, lenalidomide combined with dexamethasone (Len/Dex) is approved for use in relapsed or refractory multiple myeloma (RRMM). Our expert panel sought to provide an up-to-date practical guide on the use of lenalidomide in the managing RRMM within the Canadian clinical setting, including management of common adverse events (AEs). The panel concluded that safe, effective administration of Len/Dex treatment involves the following steps: (1) lenalidomide dose adjustment based on creatinine clearance and the extent of neutropenia or thrombocytopenia, (2) dexamethasone administered at 20-40 mg/week, and (3) continuation of treatment until disease progression or until toxicity persists despite dose reduction. Based on available evidence, the following precautions should reduce the risk of common Len/Dex AEs: (1) all patients treated with Len/Dex should receive thromboprophylaxis, (2) erythropoiesis-stimulating agents (ESAs) should be used cautiously, and (3) females of child-bearing potential and males in contact with such females must use multiple contraception methods. Finally, while Len/Dex can be administered irrespective of prior therapy and in all prognostic subsets, patients with chromosomal deletion 17(p13) have less favorable outcomes with all treatments, including Len/Dex. New directions for the use of lenalidomide in RRMM are also considered.Advances in Hematology 10/2012; 2012:621958. DOI:10.1155/2012/621958