Venous thromboembolism in myelodysplastic syndrome patients receiving lenalidomide: results from postmarketing surveillance and data mining techniques
Global Drug Safety, Celgene Corporation, Summit, New Jersey, USA. Clinical Drug Investigation
(Impact Factor: 1.56).
Multiple myeloma treatment with lenalidomide-based regimens is associated with risk of venous thromboembolism (VTE), particularly during concomitant use with erythropoiesis-stimulating agents (ESAs). The risk of VTE in myelodysplastic syndrome (MDS) patients treated with lenalidomide is not well characterized and the background risk in untreated patients is not known. This study set out to determine the reporting rate of VTE in MDS patients on lenalidomide in the two years of postmarketing experience in the US, and to investigate whether there is a disproportional signal of VTE in MDS patients on lenalidomide by screening the US FDA Adverse Event Reporting System (AERS) safety database.
The MDS population exposed to lenalidomide was obtained from RevAssist, the company's proprietary restrictive distribution programme. VTE reports were identified from the company's postmarketing surveillance safety database. The FDA AERS database was used for disproportionality analysis, and signal scores computed using three algorithms: multi-item gamma Poisson shrinker (MGPS), proportional reporting ratio (PRR), and reporting odds ratios (ROR).
A total of 7764 MDS patients were prescribed lenalidomide during the first two years of commercial use in the US. VTE representing deep vein thrombosis and pulmonary embolism was reported in 41 patients, a reporting rate of 0.53%. The computed signal scores did not exceed the statistical threshold for identification of a significant disproportional signal for VTE in MDS reports involving use of lenalidomide without concomitant use of ESAs. However, a disproportional signal of VTE was detected in MDS reports where lenalidomide was concurrently used with ESAs.
The VTE reporting rate for MDS patients receiving lenalidomide during the first two years of postmarketing exposure was low (0.53%). Disproportionality analysis demonstrated a statistically meaningful association of VTE with lenalidomide concomitantly used with ESAs in MDS patients, but the association was not statistically significant when lenalidomide was used in the absence of ESAs.
Available from: PubMed Central
- "The reported rate of DVT (VTE) for patients with MDS receiving lenalidomide during the first 2 years of post-marketing exposure has been revealed to be low (0.53%). Disproportionality analysis demonstrated a statistically meaningful correlation between VTE and lenalidomide concomitantly used with ESAs in patients with MDS; however, the correlation was not statistically significant when lenalidomide was used in the absence of ESAs (20). Of the 30 patients examined in the current study, one patient suffered from DVT in the left lower limb following three cycles of treatment, and although urokinase was administered, the thrombosis was not completely recanalised. "
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ABSTRACT: The aim of this study was to evaluate the efficacy and adverse effects of lenalidomide in the treatment of intermediate-1 risk non-5q deletion [non-del (5q)] myelodysplastic syndrome (MDS). A total of 30 patients with MDS were classified through G-banding chromosome karyotype analysis and fluorescence in situ hybridization (FISH). According to the International Prognostic Scoring System scores, among the 30 patients, 23 and seven cases had scores of 0.5 and 1.0, respectively. Lenalidomide (Revlimid(®)), 10 mg/day) was administered for 21 days every 28 days. All 30 cases were treated with lenalidomide for at least three cycles, including 20 cases with four cycles. The patients did not require erythropoietin, cyclosporine or iron chelation treatments. Statistical analysis was performed using SPSS statistical software version 13.0, and comparisons among groups were conducted using a t-test. The efficacy of lenalidomide was demonstrated in patients with intermediate-1 risk non-del (5q) MDS. Peripheral blood cell counts were improved following treatment, and absolute neutrophil, haemoglobin and platelet counts increased following 2-4 cycles of treatment. All patients became stable having undergone three cycles of treatment; however, 17 patients with chromosomal abnormalities had no cytogenetic response to the treatment, as confirmed through the FISH test. Patients with intermediate-1 risk non-del (5q) MDS treated with lenalidomide did not achieve complete haematological remission, although they demonstrated haematological improvement.
Available from: Thomas F Oltmanns
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ABSTRACT: The need for an empirically validated, dimensional system of personality disorders is becoming increasingly apparent. While a number of systems have been investigated in this regard, the five-factor model of personality has demonstrated the ability to adequately capture personality pathology. In particular, the personality disorder prototypes developed by Lynam and Widiger (2001) have been tested in a number of samples. The goal of the present study is to extend this literature by validating the prototypes in a large, representative community sample of later middle-aged adults using both self and informant reports. We found that the prototypes largely work well in this age group. Schizoid, Borderline, Histrionic, Narcissistic, and Avoidant personality disorders demonstrate good convergent validity, with a particularly strong pattern of discriminant validity for the latter four. Informant-reported prototypes show similar patterns to self reports for all analyses. This demonstrates that informants are not succumbing to halo representations of the participants, but are rather describing participants in nuanced ways. It is important that informant reports add significant predictive validity for Schizoid, Antisocial, Borderline, Histrionic, and Narcissistic personality disorders. Implications of our results and directions for future research are discussed.
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