Lenalidomide is approved in the United States for various indications, including multiple myeloma (MM), myelodysplastic syndrome associated with a deletion 5q cytogenetic abnormality and relapsed, ...

Introduction The effectiveness of patient education activities conducted within the lenalidomide and thalidomide risk evaluation and mitigation strategies (REMS) programs was evaluated by measuring understanding of serious risk and safe-use messages. Methods Results from mandatory knowledge, attitude, and behavior surveys and voluntary patient surveys completed between June 2012 and June 2013 were analyzed, and responses to questions relating to compliance with birth control measures and understanding of safe-use messages are presented by patient risk category. Results In total, 73,645 patients were enrolled into the REMS programs for lenalidomide and thalidomide and completed mandatory surveys prior to medication dispense. Of these, 2790 (3.8%) completed an additional voluntary survey. Among voluntary survey participants, for all patient pregnancy risk categories, reported compliance with birth control requirements was above 90% when starting therapy and at follow-up. At the beginning of therapy, complete compliance was 96.3%; 3 months later it was 96.4%. Patient understanding of safe-use messages was very high in all pregnancy risk groups, notably for messages repeated at each physician visit. Overall, 98.2% of patients knew that lenalidomide and thalidomide could cause birth defects, which is part of the repeated educational messaging. In contrast, 87.1% recalled that unused product should be returned to their healthcare professional, which is not included in repeated messaging. Conclusion The lenalidomide and thalidomide REMS programs enhance patient understanding of safe-use messages, resulting in high levels of compliance with the birth control precautions essential to prevent fetal exposure to these known and potential human teratogens. Overall compliance was maintained after 3 months of follow-up and throughout therapy.

INTRODUCTION:Educational brochures are an important tool for communicating risk to health-care professionals. It is important to evaluate the impact of any risk minimization tool to understand the effectiveness of the strategy. The objective of this study was to assess the effectiveness (i.e., respondents' awareness and understanding of the communication) of a targeted educational brochure distributed to health-care professionals (HCPs) as a risk minimization strategy for the communication of new rare and important adverse events (AEs).METHODS:A prospective, non-interventional, online survey was performed following distribution of a specifically designed brochure highlighting new and important adverse events to a targeted HCP population, consisting of known users of the target medicine, as represented by a commercial database. Predefined multiple-choice survey questions assessed overall HCP awareness of the brochure and understanding and retention of information in those HCPs who reported receiving the brochure.RESULTS:The educational brochure was sent to a total of 565 HCPs; 121 (21.4%) responded to the survey. The majority of respondents (95.0%) had previously prescribed or dispensed the target medicine. In all, 88 (72.7%) respondents said they had received the educational brochure, of whom 95.5% stated they had at least scanned the main points. More participants who had received the brochure (86.4% to 96.6%) answered the five individual survey questions correctly compared with those who did not (51.5% to 97.0%); this was significant for four out of five questions (P ≤ 0.005). Significantly more HCPs who received the brochure achieved the predefined pass rate (at least four of five questions answered correctly) compared with HCPs who did not receive the brochure (93.2% vs 57.6%, respectively; P = 0.000003).CONCLUSIONS:Distribution of targeted educational brochures may be an effective risk minimization strategy to raise HCP awareness of new rare and important AEs; educational brochures may also be an effective channel for sharing information on how these AEs can be best managed and on the importance and means of reporting AEs.FUNDING:Celgene Pty Ltd, Melbourne, Australia.

In Europe, a new guideline on good pharmacovigilance practices–Module II: Pharmacovigilance system master file (PSMF)—was issued, and initially came into effect on 2 July 2012, with revision on 12 April 2013. The guideline describes the PSMF, which is a detailed description of the pharmacovigilance system and supports/documents its compliance with the requirements. Establishing and maintaining a PSMF is a global activity. However, because of differences or absence of regulations, legislation or guidance documents (soft laws) across the globe, definitions of studies may be different. However, as part of the PSMF, the marketing authorisation holder in Europe should be able to produce and make available a list including data arising from all study sources (the so-called ‘study list’) for inspection, audit and Qualified Person responsible for Pharmacovigilance oversight. For medicinal products authorised in Europe, this study list should describe, on a worldwide basis, the status of each study/programme, the applicable country(ies), the product(s) and the main objective. Most importantly, it should distinguish between non-interventional and interventional studies (clinical trials) and should be organised by active substance. The study list should include all ongoing studies/programmes as well as all studies/programmes completed in the last 2 years and may be provided as an annex to the PSMF or separately. This article analyses the global impact of the new European PSMF requirements, with special focus on the mandatory global study list. There are distinct differences between biomedical research, market research, patient support programmes and non-interventional and interventional studies, and a decision tree to support classification is proposed. This decision tree should improve harmonisation of study assessment and minimise inter-country variability in the presentation of studies/programmes for the PSMF.

About half of all pregnant women are prescribed medication during their pregnancy, including drugs with teratogenic potential. There is a need to manage teratogenic risk and prevent fetal harm. In the US, risk management strategies may range from product labeling to the US Food and Drug Administration requiring a risk evaluation and mitigation strategy, including elements to assure safe use. The resources of these risk management controls on the health care system must be weighed against the benefits of preventing embryo-fetal exposure and birth defects. This article describes considerations for determining which risk mitigation strategies to use with teratogenic drugs and the challenges and opportunities to balance restrictions and burdens with the benefit of access to important drugs.

Lenalidomide (Revlimid®) is an immunomodulatory drug and an analogue of thalidomide, a known teratogen. To prevent fetal exposure, in the US lenalidomide is available only under a special restricted distribution programme called RevAssist®. Under this risk minimization programme, only prescribers and contract pharmacies registered with the programme are able to prescribe and dispense the product. Patients must be advised of, agree to and comply with the requirements of the RevAssist® programme in order to receive lenalidomide through a registered prescriber. A total of 15 584 patients were registered in the RevAssist® programme during the first year lenalidomide was on the market. There were four reports of false-positive β-human chorionic gonadotrophin measurements in patients aged 43–57 years. Mandatory patient and prescriber surveys have shown discrepant responses that were resolved by risk management intervention specialists 99% of the time. The voluntary patient surveys have shown understanding of the risks of lenalidomide use and of behaviours necessary to minimize risks in >95% of females of childbearing potential and adult males. To date, there have been no reports of pregnancy in female patients or female partners of male patients. The pharmacy audit findings showed compliance with Rev Assist® was high. Although RevAssist® is labour-intensive, time-consuming and costly, it continues to be effective in preventing fetal exposure to lenalidomide.

Celgene has developed and operated pregnancy prevention programs since 1998 with the first approval of thalidomide in the US. With the development and marketing of lenalidomide, an analog of thalidomide, the company further advanced its risk management activities, which now cover several territories across the globe. To date, the program is a success in as much as it has minimized the risk of fetal exposure and subsequent development of fetal malformations. Nonetheless, the company understands the need to provide a mechanism for intervention and remediation when at-risk behaviors are identified, and this forms an integral part of the risk management processes. The implementation of the thalidomide and lenalidomide pregnancy prevention program partners patients, healthcare professionals, regulators and the company in a spirit of shared responsibility. This paper also presents the authors' experience and perspective on the challenges of managing a pregnancy prevention program, which at its core aims at ensuring that the product's benefits outweigh the risk of fetal exposure.

Celgene has developed and operated pregnancy prevention programs since 1998 with the first approval of thalidomide in the US. With the development and marketing of lenalidomide, an analog of thalidomide, the company further advanced its risk management activities, which now cover several territories across the globe. To date, the program is a success in as much as it has minimized the risk of fetal exposure and subsequent development of fetal malformations. Nonetheless, the company understands the need to provide a mechanism for intervention and remediation when at-risk behaviors are identified, and this forms an integral part of the risk management processes. The implementation of the thalidomide and lenalidomide pregnancy prevention program partners patients, healthcare professionals, regulators and the company in a spirit of shared responsibility. This paper also presents the authors' experience and perspective on the challenges of managing a pregnancy prevention program, which at its core aims at ensuring that the product's benefits outweigh the risk of fetal exposure.

Background and objectives: 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.

7084 Background: The frequency of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) among patients with myelodysplastic syndrome (MDS) has not been characterized. This analysis describes the frequency of and risk factors for VTE among MDS patients participating in clinical studies of lenalidomide. Methods: Demographic and clinical risk factors for VTE were assessed for 408 patients with a histologically confirmed diagnosis of MDS according to FAB criteria: 45 patients in a single-center, open-label, pilot dose-finding lenalidomide study and 363 patients with low- or intermediate-1-risk MDS without (N=215) or with (N=148) a del (5q) cytogenetic abnormality and red blood cell-transfusion-dependent anemia enrolled in multi-center single-arm open-label studies. Erythropoiesis-stimulating agents were excluded in all studies. Results: VTE occurred in 14 patients during study treatment (11 DVT; 4 PE), resulting in a cumulative incidence for first VTE of 3.4% (≤365 days, 2.9%). Nine patients experienced VTE within 6 months of starting study drug (range 5–590 days; median 112.5 days). There were no differences in median age (68 vs. 72; p = 0.19) or median MDS duration at baseline (1.75 years vs. 2.40; p = 0.37) between patients with and without VTE. No differences in gender, baseline IPSS score, FAB classification, ECOG scores or number of red blood cell units transfused during the 8-week baseline period were observed (p > 0.05, all comparisons). Review of safety information identified recognized risk factors for VTE in 12/14 patients, including hospitalization (n=3), VTE history (n=3), other peripheral vascular disease (n=2), congestive heart failure/atrial fibrillation (n=4), diabetes (n=4), overweight (n=1), stroke (n=1), prior malignancy (n=2), and hormone replacement therapy (n=1). Conclusions: The incidence of VTE among MDS patients treated with lenalidomide is low. Most patients with VTE had at least one additional risk factor. Recognition of additional risk factors for VTE, with consideration of thrombosis prophylaxis where clinically warranted, is important to improve clinical outcomes in MDS patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation

Lenalidomide (Revlimid (R)) is an immunomodulatory drug and an analogue of thalidomide, a known teratogen. To prevent fetal exposure, in the US lenalidomide is available only under a special restricted distribution programme called (R) RevAssist. Under this risk minimization programme, only prescribers and contract pharmacies registered with the programme are able to prescribe and dispense the product. Patients must be advised of, agree to and comply with the requirements of the RevAssist (R) programme in order to receive lenalidomide through a registered prescriber. A total of 15 584 patients were registered in the RevAssist (R) programme during the first year lenalidomide was on the market. There were four reports of false-positive beta-human chorionic gonadotrophin measurements in patients aged 43-57 years. Mandatory patient and prescriber surveys have shown discrepant responses that were resolved by risk management intervention specialists 99% of the time. The voluntary patient surveys have shown understanding of the risks of lenalidomide use and of behaviours necessary to minimize risks in >95% of females of childbearing potential and adult males. To date, there have been no reports of pregnancy in female patients or female partners of male patients. The pharmacy audit findings showed compliance with RevAssist (R) was high. Although RevAssist (R) is labour-intensive, time-consuming and costly, it continues to be effective in preventing fetal exposure to lenalidomide.

The patient is now working full time and continues to be asymptomatic, but has mild liver function abnormalities and serologic evidence of hepatitis C, possibly related to platelet transfusions given at the time of splenectomy.His blood counts remain normal, and a peripheral-blood analysis in June 2006 showed no evidence of an abnormal lymphocyte clone.Because of the patient's young age, his initial pathology specimens were reviewed by pathologists at University of California, San Francisco (M.