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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- "Either the Cockcroft-Gault or the MDRD (modification of diet in renal disease) formula may be used to calculate creatinine clearance. Caution is urged in calculating the renal function based solely on serum creatinine level in older patients with MM . Lenalidomide treatment should be used with caution in patients with thrombocytopenia (i.e., platelet counts <50 × 10 9 /L or <30 × 10 9 /L in those with heavy marrow infiltration with myeloma) and absolute neutrophil counts <1.0 × 10 9 /L; if lenalidomide is used in this setting, measures for aggressive growth factor supplementation and/or platelet transfusion support must be in place. "
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
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ABSTRACT: Major improvement milestones in the treatment of patients with multiple myeloma (MM) include the introduction of the melphalan/prednisone combination in the 1960s; high-dose chemotherapy supported by autologous stem cell transplant in the 1980s; and the more recent introduction of the novel agents, thalidomide, lenalidomide, bortezomib, and pegylated liposomal doxorubicin. While, historically, age and eligibility for autologous stem cell transplantation were the primary basis for treatment selection, cytogenetics and other risk stratification methods are increasingly being used to guide treatment, especially with the newer agents. This trend reflects our improved understanding of the numerous genetic and biological abnormalities that mark this complex disease. In the absence of prospective, randomised studies assessing the value of risk stratification in guiding treatment decisions, and the use of the newest therapies, results of a number of studies provide a rationale for this approach. Currently available data indicate that the use of novel therapies in both the induction and maintenance settings, accompanied by risk stratification, may improve prognosis for patients with MM. Large, prospective randomised studies are needed to confirm these early pilot studies.Cancer Treatment Reviews 05/2010; 36 Suppl 2(Suppl 2):S12-7. DOI:10.1016/S0305-7372(10)70007-4 · 6.47 Impact Factor
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