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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.

Thalidomide has activity in multiple myeloma, but its use is limited by a constellation of adverse effects, most notably peripheral neuropathy. Lenalidomide, an analogue of thalidomide, does not have the toxicity profile of thalidomide. This study compared lenalidomide plus dexamethasone with placebo plus dexamethasone in the treatment of relapsed multiple myeloma. Lenalidomide plus dexamethasone was superior in all end points, including overall survival. This study compared lenalidomide plus dexamethasone with placebo plus dexamethasone in the treatment of relapsed multiple myeloma. Lenalidomide plus dexamethasone was superior in all end points, including overall survival. Multiple myeloma, the second most common hematologic cancer, caused more than 19,000 deaths in Europe in 2004. 1 To improve the outcome of treatment, new agents are needed. 2 The immunomodulatory drug thalidomide has activity in about one third of patients with relapsed or refractory multiple myeloma; response rates are increased when thalidomide is combined with dexamethasone or chemotherapy. 3 – 7 Treatment with thalidomide is associated with sedation, fatigue, constipation, rash, deep-vein thrombosis, and peripheral neuropathy. These toxic effects often require dose reduction and, in some instances, discontinuation of the drug. 8 Lenalidomide, a derivative of thalidomide, is less toxic and more potent than . . .

This randomized trial compared lenalidomide plus dexamethasone with a placebo plus dexamethasone in patients in the United States and Canada who had multiple myeloma that was resistant to one or more other treatments. The addition of lenalidomide improved the time to progression and overall survival in these patients. Important adverse events were severe neutropenia and venous thromboembolism. The addition of lenalidomide improved the time to progression and overall survival in patients with multiple myeloma. Multiple myeloma causes nearly 11,000 deaths annually in the United States. 1 Treatment with the immunomodulatory agent thalidomide or the proteasome inhibitor bortezomib has improved response rates, time to progression, and survival, but the side effects of fatigue, neuropathy, constipation, and thrombotic events remain a concern. 2 – 6 In nearly all patients who receive these drugs or other chemotherapy, the disease eventually relapses and is subsequently resistant to treatment. Lenalidomide is a thalidomide derivative that down-regulates interleukin-6 and nuclear factor κ-B and activates caspase 8 in vitro. The drug is up to 50,000 times as potent as its parent molecule in inhibiting . . .

In a study of 43 patients with low-risk myelodysplastic syndromes, lenalidomide, a thalidomide derivative, ameliorated anemia and allowed the discontinuation of transfusions in over half the patients. In patients with low-risk myelodysplastic syndromes, a thalidomide derivative ameliorated anemia and allowed the discontinuation of transfusions in over half the patients. Refractory anemia resulting from ineffective hematopoiesis is the principal therapeutic challenge for patients with myelodysplastic syndromes. 1 Recombinant erythropoietin alone or in combination with myeloid growth factors ameliorates anemia in some patients but is generally ineffective in patients who require two or more red-cell transfusions per month; its use rarely induces cytogenetic remissions. 2 , 3 Hematopoietic precursors in patients with myelodysplastic syndromes have an accelerated cell-cycle transition and impaired responsiveness to cytokine stimulation. 1 , 4 Survival signals from the microenvironment are compromised, owing in part to the presence of angiogenic molecules, disruption of the medullary architecture, and excess production of inflammatory cytokines. 5 – . . .

The combination of rituximab and lenalidomide has shown promise for the treatment of mantle-cell lymphoma (MCL) in preclinical studies. We aimed to identify the maximum tolerated dose (MTD) of lenalidomide when combined with rituximab in a phase 1 trial and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL. Patients with relapsed or refractory MCL who had received one to four previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at MD Anderson Cancer Center. In phase 1, to identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1–21 of each 28-day cycle. 375 mg/m2 intravenous rituximab was also administered in four weekly doses during cycle 1 only. In phase 2, patients received rituximab plus the MTD of lenalidomide, following the same cycles as for phase 1. Treatment in both phases continued until disease progression, stem-cell transplantation, or severe toxicity. The primary efficacy endpoint was overall response (complete or partial response). The secondary efficacy endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00294632. 52 patients were enrolled between Feb 10, 2006 and July 30, 2009, 14 in phase 1 and 44 (including six patients who received the MTD of lenalidomide in the phase 1 portion) in phase 2. The MTD was 20 mg lenalidomide. One patient who was treated with 25 mg lenalidomide developed a grade 4 non-neutropenic infection and died. In the phase 2 portion of the study, grade 3–4 haematological toxicities included neutropenia (29 patients), lymphopenia (16 patients), leucopenia (13 patients), and thrombocytopenia (ten patients). There were only two episodes of febrile neutropenia. Among 44 patients in phase 2, 25 (57%) had an overall response: 16 (36%) had a complete response and nine (20%) had a partial response. The median response duration was 18·9 months (95% CI 17·0 months to not reached [NR]). The median progression-free survival was 11·1 months (95% CI 8·3 to 24·9 months), and the median overall survival was 24·3 months (19·8 months to NR). Five of 14 patients who had received bortezomib treatment before enrolment achieved an overall response. Oral lenalidomide plus rituximab is well tolerated and effective for patients with relapsed or refractory MCL. Celgene.

To the Editor: Lenalidomide (Revlimid) is an analogue of thalidomide that has clinical activity in a variety of hematologic conditions. 1 It has recently been approved by the Food and Drug Administration for certain myelodysplastic syndromes associated with a chromosome 5q deletion. We report on the risk of thrombosis when lenalidomide is used with other agents that have known thrombogenic potential, including erythropoietin, and the need to consider antithrombotic prophylaxis when such combinations are administered. This report is based on the preliminary evaluation of results of two recently completed placebo-controlled studies, 2 identical in design, involving patients with relapsed or refractory multiple . . .

The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.

Multiple myeloma accounts for approximately 1 percent of all cancers and 10 percent of hematologic cancers. It is incurable with conventional chemotherapy. 1 Melphalan-based high-dose chemotherapy with hematopoietic stem-cell support increases the rate of complete remission and extends event-free and overall survival. 2 – 4 However, many patients still relapse, and options for salvage therapy are limited. 5 , 6 Angiogenesis is important in embryogenesis, wound healing, diabetic retinopathy, and tumor progression. 7 , 8 The immunomodulatory drug thalidomide can inhibit angiogenesis and induce apoptosis of established neovasculature in experimental models. 9 , 10 For these reasons, angiogenesis-inhibiting drugs such as thalidomide may be useful for treating cancers that . . .

To study the efficacy of daily low-dose aspirin (81 mg orally) in decreasing the incidence of venous thromboembolic events (VTEs) in patients with multiple myeloma receiving pegylated doxorubicin, vincristine, and decreased-frequency dexamethasone, plus thalidomide (DVd-T). In this phase 2 clinical trial of DVd-T, conducted by the Cleveland Clinic Foundation from August 2001 to October 2003, 105 patients were enrolled. The first 35 patients experienced increased numbers of VTEs. von Willebrand levels and platelet aggregation to ristocetin before and after treatment with DVd-T increased significantly, suggesting a pathophysiology involving platelet-endothelial interaction. Aspirin was added to the regimen, thus generating 3 patient groups: group 1 received aspirin from the start of DVd-T treatment before the study began (58 patients), group 2 received aspirin after the start of DVd-T treatment and after the study began (26 patients), and group 3 did not receive daily low-dose aspirin during the study (19 patients). Two patients being treated with warfarin for other indications were excluded from the study. The primary end point for this study was the incidence of VTE in the form of either deep venous thrombosis or pulmonary embolism. Secondary end points were the time to the first VTE, time to the composite end point of death or first VTE, and incidence of bleeding complications. After a median follow-up of 24 months, on an intent-to-treat basis, 26 posttreatment VTEs occurred after a median of 90 days, with 19% occurring in group 1, 15% in group 2, and 58% in group 3. Following multivariate time-to-event analysis, aspirin use continued to be associated with lower relative risk of VTE (hazard ratio, 0.22; confidence interval, 0.10–0.47; P<.001) and of the composite end point (hazard ratio, 0.28; confidence interval, 0.15-0.51; P<.001). Daily low-dose aspirin (81 mg orally) given to patients with newly diagnosed and relapsed/refractory multiple myeloma who were receiving DVd-T reduced the incidence of VTEs without an increase in bleeding complications.