SEARCH · PubMed Health

Results for “Lenalidomide”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed2006

Advances in oral therapy in the treatment of multiple myeloma.

Conventional IV chemotherapy regimens used for induction chemotherapy or salvage therapy in the treatment of multiple myeloma (MM) are cumbersome, with a negative impact on patient quality of life. A number of new oral drugs, including immunomodulatory agents such as thalidomide and lenalidomide, have demonstrated potent antimyeloma activity in relapsed and refractory as well as newly diagnosed MM. Clinically, response rates of 56%-72% have been reported with the combination of thalidomide and dexamethasone in patients with newly diagnosed disease; however, the combination is associated with a higher incidence of side effects, including constipation, somnolence, peripheral neuropathy, and thromboembolic complications. In contrast, preliminary safety and efficacy data from clinical studies of lenalidomide show promise. Response rates as high as 83% have been reported in patients with newly diagnosed MM, and the most common adverse event is manageable myelosuppression, which is reversible with dose reduction. Lenalidomide has different toxicities than thalidomide, exhibiting greater myelosuppression but virtually no constipation, somnolence, or peripheral neuropathy. Oncology nurses play a key role in monitoring patients for side effects and pain control and educating them about emerging treatment options. This article reviews the nursing experience with oral agents in the treatment of MM.

Administration, Oral↗

PubMed2006

Clinical management of myelodysplastic syndromes with interstitial deletion of chromosome 5q.

Deletions of the long (q) arm of chromosome 5 [del(5q)]occur in patients with myelodysplastic syndromes (MDS) including, but not limited to, those who meet the WHO definition of the 5q- syndrome. Del(5q) MDS patients frequently have symptomatic anemia, and its treatment has traditionally consisted of RBC transfusions and, for some, iron chelation therapy. Erythropoietin, darbepoetin, hypomethylating agents, and lenalidomide can enhance erythropoiesis in MDS patients with anemia, increasing hemoglobin levels and abrogating RBC transfusion requirements. Lenalidomide is particularly active in treating the anemia of del(5q) MDS, which is especially relevant given the low response rate to erythropoietin in this group of patients. In a recent study of 43 MDS patients, 10 of 12 patients (83%) with del(5q) MDS achieved sustained RBC transfusion independence (or a > 2 g/dL increase in hemoglobin), compared with 57% of those with a normal karyotype and 12% of those with other karyotypic abnormalities. Complete cytogenetic remissions were achieved in 75% (nine of 12) of the del(5q) MDS patients, suggesting that lenalidomide targets a fundamental pathogenetic feature of MDS that is more pronounced in the presence of chromosomal 5q deletions. This review highlights some issues about the classification and treatment of del(5q) MDS.

Anemia, Hypochromic↗

PubMed2006

Thromboembolism risk reduction in multiple myeloma patients treated with immunomodulatory drug combinations.

Deep vein thrombosis and its lethal complication pulmonary embolism are manifestations of venous thromboembolism (VTE), which is typically associated with cancer and recent major surgery. Certain solid tumors and hematologic malignancies impose an inherently elevated risk of VTE that is compounded by chemotherapy and other risk factors. Multiple myeloma (MM) and other plasma cell dyscrasias are thrombogenic as a consequence of their multiple hemostatic effects, including elevated interleukin-6 levels, pro-coagulant antibody formation, paraprotein interference with fibrin structure, activated protein C resistance, and endothelial damage. The oral immunomodulatory drugs thalidomide and lenalidomide have produced major therapeutic responses in patients with MM when used in combination with oral steroids and chemotherapy, but a high incidence of VTE has been reported. Various VTE prophylaxis strategies with thalidomide- and lenalidomide-containing combinations have been investigated in clinical studies. This review discusses emerging results on the use of VTE prophylaxis to minimize VTE risks associated with MM treatment regimens containing thalidomide and lenalidomide.

Anticoagulants↗

PubMed2006

[New drugs for myeloma].

Thalidomide, administered orally, bortezomib (Velcade) intravenously and lenalidomide (Revlimid), also orally, are three agents that act on myeloma relapse. Thalidomide acts by a variety of mechanisms and is toxic to the peripheral nervous system as well as teratogenic. It acts in synergy with dexamethasone. Recent results prove that its use as first-line treatment combined with oral conventional "MP" chemotherapy improves survival in patients older than 65 years. Its use as first-line treatment with this chemotherapy appears likely. Bortezomib is the first drug in the proteasome inhibitor class. It too is toxic to the peripheral nervous system and synergistic with dexamethasone. Several studies show its efficacy as first-line 'induction treatment' with dexamethasone, in patients to receive a subsequent autologous stem cell transplantation. The combination of bortezomib and "MP" is also promising. Lenalidomide, a structural analog of thalidomide, is effective in relapsing patients. Its toxicity is essentially hematologic. It is also synergistic with dexamethasone and promising as first-line treatment. These different drugs can be used successively at relapse, making myeloma a chronic disease. They can also be used together for greater effectiveness. These combinations will replace conventional chemotherapies in the future.

Antineoplastic Agents↗

PubMed2006

Biological and prognostic significance of chromosome 5q deletions in myeloid malignancies.

The presence of del(5q), either as the sole karyotypic abnormality or as part of a more complex karyotype, has distinct clinical implications for myelodysplastic syndromes (MDS) and acute myeloid leukemia. The 5q- syndrome, a subtype of low-risk MDS, is characterized by an isolated 5q deletion and <5% blasts in the bone marrow and can serve as a useful model for studying the role of 5q deletions in the pathogenesis and prognosis of myeloid malignancies. Recent clinical results with lenalidomide, an oral immunomodulatory drug, have shown durable erythroid responses, including transfusion independence and complete cytogenetic remissions in patients with del(5q) MDS with or without additional chromosomal abnormalities. These results indicate that lenalidomide can overcome the pathogenic effect of 5q deletion in MDS and restore bone marrow balance. The data provide important new insights into the pathobiology of 5q chromosomal deletions in myeloid malignancies.

Chromosome Deletion↗

PubMed2005

Properties of thalidomide and its analogues: implications for anticancer therapy.

Thalidomide and its immunomodulatory (IMiDs) analogs (lenalidomide, Revlimid, CC-5013; CC-4047, ACTIMID) are a novel class of compounds with numerous effects on the body's immune system, some of which are thought to mediate the anticancer and anti-inflammatory results observed in humans. Thalidomide is currently being used experimentally to treat various cancers and inflammatory diseases. It is approved for the treatment of dermal reaction from leprosy and is currently in phase III trials for multiple myeloma. Thalidomide and IMiDs inhibit the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukins (IL) 1beta, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity thereby increasing the T cells' anticancer activity. They induce an IL-2-mediated primary T cell proliferation with a concomitant increase in IFN-gamma production and decrease the density of TNF-alpha-induced cell surface adhesion molecules ICAM-1, VCAM-1, and E-selectin on human umbilical vein endothelial cells. Thalidomide stimulates the Th-1 response increasing IFN-gamma levels while CC-4047 increased IL-2 as well. Some of the above immunomodulatory activities along with anti-angiogenic, anti-proliferative, and pro-apoptotic properties are thought to mediate the IMiDs' antitumor responses observed in relapsed and refractory multiple myeloma and some solid tumor cancers. This has led to their use in various oncology clinical trials. The second generation IMiD, lenalidomide, has shown potential in treating the bone marrow disorders myelodysplastic syndrome and multiple myeloma. It is currently in phase II and III trials for these diseases respectively with numerous phase II trials in other hematologic and solid tumors.

Angiogenesis Inhibitors↗

PubMed2006

Immunomodulatory drugs in myelodysplastic syndromes.

This review summarises the mechanism of action of immunomodulatory analogues of thalidomide and their use in myelodysplastic syndromes. Thalidomide was found to have a response rate of approximately 20% in these patients. Lenalidomide--which is more potent and less toxic than thalidomide--has been used in three clinical trials and produced the best responses (60 - > 90%) in low- and intermediate-1-risk transfusion-dependent patients with del(5q). The responses are purely erythroid in nature, and are associated with major cytogenetic responses in > 50% of the del(5q) patients. Non-del(5q) low- and intermediate-1-risk transfusion-dependent patients also had a approximately 25% incidence of transfusion independence following therapy with lenalidomide. Median time to response is approximately 4 weeks and 90% of patients respond within 12 weeks. The precise mechanism of action remains unknown but anticytokine, antiangiogenic and immunomodulatory properties are thought to play a role.

Adult↗

PubMed2006

Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma.

Immunomodulatory drugs, such as thalidomide, lenalidomide (Revlimid, CC-5013) and actimid (CC-4047), have a broad spectrum of activity and have shown remarkable responses in patients with multiple myeloma and related hematological diseases, such as myelodysplastic syndrome. They are currently being tested in other cancer types. This review will focus on the preclinical and clinical activity of thalidomide and its more potent immunomodulatory derivatives that are used to treat multiple myeloma. They represent a new class of antitumor agents that not only target the tumor cell directly, but also have significant activity within the bone marrow milieu. These agents have shown high responses in all phases of multiple myeloma, including the upfront setting, relapsed refractory stage and also as maintenance therapy for the disease. They have been used in combination with dexamethasone, chemotherapy and, more recently, with other novel agents, such as proteasome inhibitors. Thalidomide and lenalidomide in combination with dexamethasone have recently been approved by the US FDA for the treatment of multiple myeloma.

Adjuvants, Immunologic↗

PubMed2005

New treatments for multiple myeloma.

In 2004, multiple myeloma was diagnosed in more than 15,000 people in the United States and will account for approximately 20% of deaths due to hematologic malignancies. Although traditional therapies such as melphalan (Alkeran)/prednisone, combination chemotherapy with VAD (vincristine, doxorubicin [Adriamycin], and dexamethasone), and high-dose chemotherapy with stem cell transplantation have shown some success, median survival remains between 3 to 5 years. Treatment options for patients with multiple myeloma have increased in recent years, with the promise of improvement in survival. New agents, such as the proteasome inhibitor bortezomib (Velcade), the antiangiogenic and immunomodulator thalidomide (Thalomid) and its analogs, such as lenalidomide (Revlimid), together with other small molecules, including arsenic trioxide (Trisenox), and other targeted therapies, have been studied alone and in combination with other antineoplastic therapies, either as induction therapy prior to stem cell transplantation or in patients with relapsed disease. Bortezomib recently was approved in the United States for the treatment of multiple myeloma in patients who have received at least one prior therapy. The use of bortezomib-based regimens as front-line therapy as well as the use of other agents in multiple myeloma remain under investigation, and approvals for both thalidomide and lenalidomide are hoped for soon, with the overall prospect of patient outcome continuing to be increasingly positive.

Antineoplastic Agents↗

PubMed2006

Myelodysplasia: when to treat and how.

Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells characterized by ineffective hematopoiesis. The result is pancytopenia leading to transfusion-dependent anemia, an increased risk of infection or bleeding, and a potential to progress to acute myeloid leukemia (AML). MDS is most prevalent among older individuals, many of whom also suffer from other medical conditions. MDS is classified according to World Health Organization criteria and the International Prognostic Scoring System. Supportive care remains the mainstay of therapy. Those with low-risk MDS can often be monitored for an extended period of time without specific therapy, whereas those with intermediate- or high-risk MDS benefit from treatment. Currently, only azacitidine is approved for the treatment of MDS. Several new agents are being tested, including inhibitors of angiogenesis (thalidomide, lenalidomide), farnesyl transferase inhibitors (lonafarnib, tipifarnib), and DNA methyltransferase inhibitors (azacitidine, decitabine). Lenalidomide appears particularly effective in patients with low-risk MDS with the deletion of chromosome 5q31. Allogeneic stem cell transplantation is an alternative for high-risk MDS. With advances in transplantation techniques, this treatment can be offered to an increasing number of patients. However, it is necessary to assess each patient's disease individually and to evaluate prognostic factors, other treatment options, and the appropriateness and timing of transplantation.

Anemia↗

PubMed2006

Immunomodulatory drugs as a therapy for multiple myeloma.

Thalidomide and the analogues lenalidomide (CC-5013, Revlimid) and CC-4047 (Actimid) belong to the family of immunomodulatory drugs (IMiDs). These agents have anti-angiogenic properties, modulate TNFalpha and IL-12 secretion, co-stimulate T cells, increase NK cell toxicity and have direct anti-tumour effects. These characteristics have made of them promising drugs for treatment of relapsed, refractory and newly diagnosed MM. It seems that lenalidomide and CC-4047 are more powerful in inhibiting TNFalpha and have, except for myelosuppression, less side effects than Thal. Combination of IMiDs with dexamethasone, bortezomib and with chemotherapeutic agents are tested in numerous trials, which will help in determining the optimal combination and administration schedule of different molecules to take advantage of non-overlapping toxicities and synergisms between those agents.

Animals↗

PubMed2006

Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of numerous inflammatory and autoimmune disorders. Accordingly, TNF-alpha inhibitors, such as thalidomide, infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel), have been used with success in the treatment of autoimmune disorders, including psoriasis, rheumatoid arthritis, inflammatory bowel diseases, and lymphoproliferative disorders. Although anti-TNF-alpha therapy is safe and well tolerated, various adverse cutaneous reactions have been reported. OBSERVATIONS: We encountered 5 patients who developed erythematous annular plaques on the trunk and extremities while receiving 4 different medications with inhibitory activity against TNF-alpha. One patient was treated with lenalidomide (Revlimid) for multiple myeloma, 2 received infliximab, and 1 received etanercept for severe rheumatoid arthritis; the last patient was in a clinical trial of adalimumab for psoriatic arthritis. Skin biopsy specimens revealed diffuse interstitial granulomatous infiltrates of lymphocytes, histiocytes, and eosinophils, palisading degenerated collagen. Withdrawal of the medications led to complete resolution of the skin lesions. CONCLUSION: Interstitial granulomatous dermatitis should be considered in the differential diagnosis of skin lesions occurring in the setting of anti-TNF-alpha therapy.

Adalimumab↗

PubMed2006

Evaluation of recurring cytogenetic abnormalities in the treatment of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are clinically heterogeneous, but the presence of specific cytogenetic abnormalities can predict disease manifestations, provide a basis for prognosis, and direct treatment. Conventional cytogenetic analysis is instrumental in identifying chromosomal abnormalities in MDS and novel genetic methods may provide supplementary information. Treatment with lenalidomide was recently shown to be effective in MDS, particularly in those cases with del(5q), resulting in durable cytogenetic remission and hematological responses. In this paradigm, diagnosis of the del(5q) abnormality would be essential to predicting response to therapy.

Chromosome Aberrations↗

PubMed2006

[The plasma cell myeloma--molecular pathogenesis and target therapies].

The cells of the malignant clone of plasmacell myeloma have cytogenetic aberrations in a substantial number of cases. Many of these abnormal karyotypes are predictive for an unfavorable outcome. Gene mutations and abnormal gene expression, particularly of oncogenes and tumor suppressor genes, are often observed in myeloma cells. The cross talk between the myeloma cells and the bone marrow microenvironment plays an important role for growth and survival of the tumor cells. As a consequence of this cell-to-cell-interaction, several cytokines are secreted. The intracellular signaling, evoked by these cytokines, leads to continuous growth and proliferation and inhibition of apoptosis. Since these molecular pathways have been defined, many new targets for therapeutical interventions become obvious. Some molecules, directed against cytokines, are under early clinical investigation. Medicaments intervening in the cross talk between the myeloma cell and the bone marrow stroma as Thalidomide, Lenalidomide or Bortezomib are already available. Many of the myeloma patients suffer from bone disease. Some new drugs inhibiting the differentiation and activation of osteoclasts are evaluated in clinical trials. These molecules will be an important contribution against the painful bone disease of plasmacell myeloma.

Aged↗

PubMed2005

Treatment paradigms for the newly diagnosed patient with multiple myeloma.

The management of newly diagnosed multiple myeloma is currently being revolutionized by the emergence of novel therapeutic agents. Thalidomide, the thalidomide analogue lenalidomide, and the proteasome inhibitor bortezomib each have potential roles to play in the initial therapy of myeloma that are supported by encouraging clinical trials results. While evaluation for stem cell transplantation (SCT) remains a part of the algorithm for management of the newly diagnosed patient, these drugs offer improved options for induction before, and possibly maintenance after, SCT. For the patient who is not a candidate for SCT the armamentarium for management has been significantly expanded. This review will summarize currently available data regarding these exciting agents and will describe therapeutic strategies currently on the horizon.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Immunomodulatory drugs.

After nearly decades of extinction as a sedative and antiemetic, thalidomide reemerged as the parent compound of a novel and promising class of therapeutics termed the immunomodulatory drugs (IMiDs). The analogues of thalidomide, CC-5013 (lenalidomide, Revlimid) and CC-4047 (Actimid) are more potent regulators of cellular immune and cytokine response while lacking some of the dose limiting side effects of the parent compound, such as neurologic toxicity. Preclinical data will be reviewed that outlines these drugs' effects on tumor necrosis alpha, interleukin 12, angiogenesis, and T-cell function. The evolution of the use of thalidomide as a therapeutic for diseases such as multiple myeloma and myelodysplastic syndrome and the promising initial results of the new IMiDs will be reviewed.

Humans↗

PubMed2006

Treatment of multiple myeloma: an emphasis on new developments.

Not all patients who fulfill the minimal criteria for diagnosis of multiple myeloma should be treated. If doubt exists about beginning therapy, one should wait and re-evaluate the patient in 2 or 3 months. There is no evidence that early treatment of multiple myeloma is advantageous. All patients should be considered possible candidates for an autologous stem cell transplantation. If they are deemed to be eligible, they should be treated for 3 to 4 months with therapy that does not damage the hematopoietic stem cells. Currently, most physicians use thalidomide plus dexamethasone or dexamethasone alone for induction. Vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) have been used in the past. Autologous stem cell transplantation prolongs disease-free survival and overall survival. The treatment-related mortality rate is 1% to 2%. Melphalan, 200 mg/m2, is the most widely used preparative regimen. Although allogeneic transplantation is attractive, the mortality rate (about 20%) is too high to recommend conventional allogeneic transplantation. Non-myeloablative transplantation is currently under investigation. If the patient is not a candidate for autologous stem cell transplantation, therapy with melphalan and prednisone is a good choice. Patients with relapsed or refractory disease may be treated with dexamethasone, thalidomide and dexamethasone, bortezomib (Velcade, PS-341), or lenalidomide (Revlimid, not yet approved by the Food and Drug Administration).

Angiogenesis Inhibitors↗

PubMed2006

Current status of new drugs for the treatment of patients with multiple myeloma.

Multiple myeloma, a malignant disorder of plasma cells, is the second most common haematological malignancy. Although treatable, multiple myeloma remains incurable in virtually all cases, with a median survival of 3-4 years. Fortunately for patients with this disease, traditional treatment paradigms have been challenged with the emergence of a number of new therapies entering clinical practice over the last 6 years. In this review, we focus on the use of thalidomide (Thalidomide Pharmion; Boulder, CO, USA), lenalidomide (Revlimid; Celgene Corporation, Summit, NJ, USA) and bortezomib (Velcade; Janssen Pharmaceutica N.V., Belgium) in the treatment of myeloma. We present the current clinical experience with respect to efficacy and toxicity of these promising new agents and how the incorporation of these drugs with traditional therapies may improve the outcome for patients with multiple myeloma.

Antineoplastic Agents↗