Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes

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Abstract

Lenalidomide, an oral immunomodulatory agent, has received approval in the USA from the Food and Drug Administration (FDA) for the management of myelodysplastic syndromes (MDS) classified by the International Prognostic Scoring System (IPSS) as low risk or intermediate-1 risk and with a deletion 5q (del(5q)) cytogenetic abnormality. Although some patients with del(5q) have a relatively good prognosis, all del(5q) patients will become transfusion-dependent at some point during the course of their disease. The results of two clinical trials in more than 160 patients with MDS have demonstrated clear therapeutic benefits of lenalidomide, with >60% of patients achieving independence from transfusion during therapy, irrespective of age, prior therapy, sex, or disease-risk assessment. The recommendations presented in this review will aid the safe administration of lenalidomide for the treatment of patients with low-risk or intermediate-1-risk MDS and a del(5q) cytogenetic abnormality, and they will help physicians avoid unnecessary dose reduction or interruption, thus assuring the best efficacy for patients.

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Most cited references 13

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International scoring system for evaluating prognosis in myelodysplastic syndromes.

P. Greenberg, C. Cox, M M LeBeau … (1997)

Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.

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New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients.

Detlef Haase, Ulrich Germing, Julie Schanz … (2007)

We have generated a large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) at 4 institutions in Austria and 4 in Germany. Cytogenetic analyses were successfully performed in 2072 (97.6%) patients, revealing clonal abnormalities in 1084 (52.3%) patients. Numeric and structural chromosomal abnormalities were documented for each patient and subdivided further according to the number of additional abnormalities. Thus, 684 different cytogenetic categories were identified. The impact of the karyotype on the natural course of the disease was studied in 1286 patients treated with supportive care only. Median survival was 53.4 months for patients with normal karyotypes (n = 612) and 8.7 months for those with complex anomalies (n = 166). A total of 13 rare abnormalities were identified with good (+1/+1q, t(1q), t(7q), del(9q), del(12p), chromosome 15 anomalies, t(17q), monosomy 21, trisomy 21, and -X), intermediate (del(11q), chromosome 19 anomalies), or poor (t(5q)) prognostic impact, respectively. The prognostic relevance of additional abnormalities varied considerably depending on the chromosomes affected. For all World Health Organization (WHO) and French-American-British (FAB) classification system subtypes, the karyotype provided additional prognostic information. Our analyses offer new insights into the prognostic significance of rare chromosomal abnormalities and specific karyotypic combinations in MDS.

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Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study.

W O'Fallon, L. Joseph Melton, Christine M. Lohse … (2002)

To assess the potential impact of controlling risk factors on the incidence of venous thromboembolism by estimating the population attributable risk (defined as the percentage of all cases of a disease in a population that can be "attributed" to a risk factor) for deep vein thrombosis and pulmonary embolism associated with venous thromboembolism risk factors. Using data from a population-based, nested, case-control study of the 625 Olmsted County, Minnesota, residents with a definite first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 15-year period 1976 to 1990 and 625 unaffected Olmsted County residents matched for age and sex, we developed a conditional logistic regression model appropriate to the matched case-control study design and then estimated attributable risk for the risk factors individually and collectively. Fifty-nine percent of the cases of venous thromboembolism in the community could be attributed to institutionalization (current or recent hospitalization or nursing home residence). Hospitalization for surgery (24%) and for medical illness (22%) accounted for a similar proportion of the cases, while nursing home residence accounted for 13%. The individual attributable risk estimates for malignant neoplasm, trauma, congestive heart failure, central venous catheter or pacemaker placement, neurological disease with extremity paresis, and superficial vein thrombosis were 18%, 12%, 10%, 9%, 7%, and 5%, respectively. Together, the 8 risk factors accounted for 74% of disease occurrence. Factors associated with institutionalization independently account for more than 50% of all cases of venous thromboembolism in the community. Greater emphasis should be placed on prophylaxis for hospitalized medical patients. Other recognized risk factors account for about 25% of all cases of venous thromboembolism, while the remaining 25% of cases are idiopathic.

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Author and article information

Contributors

: +49-203-5460 , +49-203-5462249 , gia@krebs-duisburg.de

Journal

Journal ID (nlm-ta): Ann Hematol

Title: Annals of Hematology

Publisher: Springer-Verlag (Berlin/Heidelberg )

ISSN (Print): 0939-5555

ISSN (Electronic): 1432-0584

Publication date (Electronic): 12 February 2008

Publication date (Print): May 2008

Volume: 87

Issue: 5

Pages: 345-352

Affiliations

[1 ]St. Johannes Hospital, Medizinische Klinik II, An der Abtei 7-11, 47166 Duisburg, Germany

[2 ]Service d’Hématologie Clinique, Hôpital Avicenne (AP-HP), Université Paris 13, Bobigny, France

[3 ]Department of Haematology, King’s College Hospital, London, UK

[4 ]Medical Center, Department of Hematology, Radboud University Nijmegen, Nijmegen, Netherlands

[5 ]Medizinische Klinik und Poliklinik I, University Clinic Carl Gustav Carus, Dresden, Germany

[6 ]Hematology Department, Hospital Universitario La Fe, Valencia, Spain

[7 ]Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN USA

[8 ]BMTU, Gledhow Wing, St. James’s University Hospital, Leeds Teaching Hospitals, Leeds, UK

[9 ]Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON Canada

Article

Publisher ID: 449

DOI: 10.1007/s00277-008-0449-0

PMC ID: 2275303

PubMed ID: 18265982

SO-VID: 340f902e-566e-48fe-8427-c5108eadf98a

History

Date received : 22 December 2007

Date accepted : 17 January 2008

Custom metadata

ScienceOpen disciplines: Hematology

Keywords: treatment guidelines,mds,lenalidomide,myelodysplastic syndromes

Data availability:

ScienceOpen disciplines: Hematology

Keywords: treatment guidelines, mds, lenalidomide, myelodysplastic syndromes

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