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      The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function

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          Abstract

          BACKGROUND:

          In patients with multiple myeloma, renal impairment (RI) at the time of diagnosis is associated with poor survival. To the authors' knowledge, the current retrospective analysis presented is the first to assess the impact of various degrees of renal dysfunction on safety and efficacy outcomes in a large cohort of patients with relapsed and/or refractory multiple myeloma who received treatment with lenalidomide plus dexamethasone.

          METHODS:

          Three hundred fifty-three patients from 2 large phase 3 trials were randomized to receive lenalidomide (25 mg) plus dexamethasone (40 mg). For the purpose of this analysis, RI was defined according to the calculated creatinine clearance (CL Cr) level as follows: mild or no RI (CL Cr ≥ 60 mL/minute), moderate RI (CL Cr from ≥ 30 mL/minute to <60 mL/minute), and severe RI (CL Cr <30 mL/minute).

          RESULTS:

          The RI subgroups did not differ significantly in terms of the overall response rate (range, 50%-64%) or response quality (very good partial response or better, 27%-37%). In all RI subgroups, the time to progression and progression-free survival did not differ significantly compared with the mild or no RI group. Patients with RI experienced an increased incidence of thrombocytopenia, required more frequent lenalidomide dose reduction or interruption, and had shorter overall survival than patients with mild or no RI ( P = .006). Lenalidomide plus dexamethasone led to improvement in renal function in the majority of patients.

          CONCLUSIONS:

          The results from this study indicated that, with careful monitoring of the CL Cr level and adverse events as well as appropriate dose adjustments, lenalidomide plus dexamethasone is an effective and well tolerated treatment option for patients with multiple myeloma who have RI. Cancer 2010. © 2010 American Cancer Society.

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          Most cited references16

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          Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant.

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            Pathogenesis and treatment of renal failure in multiple myeloma.

            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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              Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group.

              The purpose of the present study was to analyse the importance and prognostic value of renal failure in multiple myeloma patients. The frequency and reversibility of renal failure in 775 multiple myeloma patients diagnosed between 1984-86 and 1990-92 in the Nordic countries were studied. Renal failure, defined as plasma creatinine > 130 micromol/l, was observed in 29% of the cases at the time of diagnosis. During the first year after diagnosis 58% achieved normalisation of p-creatinine, and this was achieved mainly during the first 3 months. Reversibility of renal failure was more frequently observed in patients with moderate renal failure, hypercalcaemia and low Bence-Jones protein excretion. In a multivariate analysis renal failure, high age, stage III disease and hypercalcaemia were independent prognostic factors for survival. Patients who needed dialysis had a poor prognosis, with a median survival of 3.5 months. A 12-months landmark analysis showed that reversibility of renal failure was a more important prognostic factor than response to chemotherapy. It is concluded that renal failure in multiple myeloma is reversible in about half the cases, and reversibility of renal failure improves long-term survival.
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                Author and article information

                Journal
                Cancer
                cncr
                Cancer
                Wiley Subscription Services, Inc., A Wiley Company
                0008-543X
                1097-0142
                15 August 2010
                24 May 2010
                : 116
                : 16
                : 3807-3814
                Affiliations
                [1 ]simpleDepartment of Clinical Therapeutics, University of Athens School of Medicine Athens, Greece
                [2 ]simpleHematology Department, Princess University Hospital Madrid, Spain
                [3 ]simpleAbramson Cancer Center, University of Pennsylvania Philadelphia, Pennsylvania
                [4 ]simpleDepartment of Internal Medicine V, University of Heidelberg Heidelberg, Germany
                [5 ]simpleKarmanos Cancer Institute, Wayne State University Detroit, Michigan
                [6 ]simpleDepartment of Medical Oncology, Duke University Medical Center Durham, North Carolina
                [7 ]simpleInstitute of Blood Pathology and Transfusion Medicine, Hematology Department of the Academy of Medical Sciences of Ukraine Lviv, Ukraine
                [8 ]simpleDivision of Hematology-Oncology, Princess Margaret Hospital Toronto, Ontario, Canada
                [9 ]simpleClinical Research and Development, Oncology, Celgene Corporation Summit, New Jersey
                [10 ]simpleDepartment of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center Houston, Texas
                Author notes
                Corresponding author: Meletios Dimopoulos, MD, Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra Hospital, 80 Vas. Sofias, 11528 Athens, Greece; Fax: (011) 30-210-3381511; mdimop@ 123456med.uoa.gr

                Meletios Dimopoulos, Donna M. Weber, and Marta Olesnyckyj designed the study; Meletios Dimopoulos and Donna M. Weber wrote the report for the study; Adrian Alegre, Edward A. Stadtmauer, Hartmut Goldschmidt, Jeffrey A. Zonder, Carlos M. de Castro, Zvenyslava Masliak, Donna Reece, and Meletios Dimopoulos recruited patients for the study; and Zhinuan Yu performed the statistical analyses. All authors were involved in analyzing and interpreting the data and critically reviewing the article content. The authors were fully responsible for content and editorial decisions for this article.

                Article
                10.1002/cncr.25139
                2970911
                20564094
                9a549450-4970-4319-8c46-1dbc11384773
                Copyright © 2010 American Cancer Society

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 03 November 2009
                : 03 November 2009
                : 03 November 2009
                Categories
                Original Article

                Oncology & Radiotherapy
                renal impairment,multiple myeloma,lenalidomide,dexamethasone,creatinine clearance

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