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 37 records · Page 2Linked to original sources

PubMed2006

Role of lenalidomide in the treatment of multiple myeloma and myelodysplastic syndrome.

OBJECTIVE: To evaluate lenalidomide in the treatment of multiple myeloma and myelodysplastic syndrome (MDS). DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-August 2005), Science Citation Index (1980-August 2005), and Proceedings of the American Society of Hematology (2000-2004). DATA SYNTHESIS: New analogs of thalidomide have been synthesized that are more potent and less toxic. Lenalidomide (CC-5013) is currently in Phase III trials for the treatment of multiple myeloma and MDS. Phase II trials demonstrated lenalidomide's efficacy in patients refractory to thalidomide. The full potential of this agent has yet to be proven, but preliminary data seem promising. CONCLUSIONS: Lenalidomide is a potent immunomodulating drug that offers different mechanisms of action and therapeutic potential for the treatment of multiple myeloma, MDS, and other malignancies.

Animals↗

PubMed2005

Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup.

The survival of patients with myelodysplastic syndromes is strongly affected by chromosomal abnormalities. Patients with an isolated del(5q31) have a favourable prognosis that worsens with the addition of another chromosomal abnormality. It has been reported that both patients with isolated del(5q31) and those with one single additional chromosomal abnormality achieve hematological and cytogenetic remissions with lenalidomide therapy. Whether this translates into improved overall survival of the patient population is unclear. We analysed data of 25 patients with myelodysplastic syndrome and complex chromosomal abnormalities including del(5q31) and show that their median survival is between 7 and 8 months, irrespective of the medullary blast count. Furthermore, we present data of a patient with complex karyotypic anomalies inclusive of del(5q31) treated with lenalidomide who achieved complete cytogenetic remission. This cytogenetic remission was diagnosed after 6 months, and the hematological response is ongoing at 9 months of therapy at a dose of 5 mg p.o. daily. We conclude that lenalidomide has the potential to induce sustained hematological and cytogenetic remissions in the poor prognosis MDS subgroup of del(5q31) patients with complex chromosomal anomalies and that this is likely to improve overall survival.

Adult↗

PubMed2006

Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide: phase I clinical trial of three dosing schedules in patients with solid malignancies.

Thalidomide is an anti-angiogenic agent currently used to treat patients with malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an immunomodulatory thalidomide analogue licensed in the United States of America (USA) for the treatment of a subtype of myelodysplastic syndrome. This two-centre, open-label phase I study evaluated dose-limiting toxicities in 55 patients with malignant solid tumours refractory to standard chemotherapies. Lenalidomide capsules were consumed once daily for 12 weeks according to one of the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25mg daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3 cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study period. Two patients experienced a grade 3 hypersensitivity rash. Four patients in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2 patients with predisposing medical factors, grade 3 cardiac dysrhythmia was recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two partial radiological responses were measured by computed tomography scanning; 8 patients had stable disease after 12 weeks of treatment. Fifteen patients remained on treatment as named patients; 1 with metastatic melanoma remains in clinical remission 3.5 years from trial entry. This study indicates the tolerability and potential clinical efficacy of lenalidomide in patients with advanced solid tumours who have previously received multi-modality treatment. Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or (III) are advocated for large-scale trials of long-term administration.

Adult↗

PubMed2005

Efficacy of lenalidomide in myelodysplastic syndromes.

BACKGROUND: Ineffective erythropoiesis is the hallmark of myelodysplastic syndromes. Management of the anemia caused by ineffective erythropoiesis is difficult. In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the safety and hematologic activity of lenalidomide, a novel analogue of thalidomide. METHODS: Forty-three patients with transfusion-dependent or symptomatic anemia received lenalidomide at doses of 25 or 10 mg per day or of 10 mg per day for 21 days of every 28-day cycle. All patients either had had no response to recombinant erythropoietin or had a high endogenous erythropoietin level with a low probability of benefit from such therapy. The response to treatment was assessed after 16 weeks. RESULTS: Neutropenia and thrombocytopenia, the most common adverse events, with respective frequencies of 65 percent and 74 percent, necessitated the interruption of treatment or a dose reduction in 25 patients (58 percent). Other adverse events were mild and infrequent. Twenty-four patients had a response (56 percent): 20 had sustained independence from transfusion, 1 had an increase in the hemoglobin level of more than 2 g per deciliter, and 3 had more than a 50 percent reduction in the need for transfusions. The response rate was highest among patients with a clonal interstitial deletion involving chromosome 5q31.1 (83 percent, as compared with 57 percent among those with a normal karyotype and 12 percent among those with other karyotypic abnormalities; P=0.007) and patients with lower prognostic risk. Of 20 patients with karyotypic abnormalities, 11 had at least a 50 percent reduction in abnormal cells in metaphase, including 10 (50 percent) with a complete cytogenetic remission. After a median follow-up of 81 weeks, the median duration of transfusion independence had not been reached and the median hemoglobin level was 13.2 g per deciliter (range, 11.5 to 15.8). CONCLUSIONS: Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy.

Adult↗

PubMed2006

Lenalidomide therapy in myelofibrosis with myeloid metaplasia.

We present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.

Administration, Oral↗

PubMed2006

Thalidomide and lenalidomide extend survival in a transgenic mouse model of amyotrophic lateral sclerosis.

Accumulating evidence suggests that inflammation plays a major role in the pathogenesis of motor neuron death in amyotrophic lateral sclerosis (ALS). Important mediators of inflammation such as the cytokine tumor necrosis factor-alpha (TNF-alpha) and its superfamily member fibroblast-associated cell-surface ligand (FasL) have been implicated in apoptosis. We found increased TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS patients and G93A transgenic mice. Both increased TNF-alpha and FasL immunostaining in the lumbar spinal cord of the G93A SOD1 transgenic mice occurred at 40-60 d, well before the onset of symptoms and loss of motor neurons. We tested the neuroprotective effect of thalidomide and its analog lenalidomide, pharmacological agents that inhibit the expression of TNF-alpha and other cytokines by destabilizing their mRNA. Treatment with either thalidomide or lenalidomide attenuated weight loss, enhanced motor performance, decreased motor neuron cell death, and significantly increased the life span in G93A transgenic mice. Treated G93A mice showed a reduction in TNF-alpha and FasL immunoreactivity as well as their mRNA in the lumbar spinal cord. Both compounds also reduced interleukin (IL)-12p40, IL-1alpha, and IL-1beta and increased IL-RA and TGF-beta1 mRNA. Therefore, both thalidomide and lenalidomide bear promise as therapeutic interventions for the treatment of ALS.

Adult↗

PubMed2006

Lenalidomide in multiple myeloma.

Current therapies for multiple myeloma include steroids, alkylating agents and high-dose chemotherapy with autologous stem cell transplant. These approaches are typically associated with initially good response rates, but they ultimately fail as a result of disease progression. New therapies that overcome resistance, lower toxicity and maintain remission are needed. Recent advances in the treatment of multiple myeloma include bortezomib and thalidomide. Lenalidomide (Revlimid) is an immunomodulatory drug that has undergone rapid clinical development in multiple myeloma and was recently approved by the US FDA for use in patients with relapsed disease. Clinical trials demonstrate that lenalidomide, particularly in combination with dexamethasone, produces durable clinical responses in patients with relapsed and refractory disease and is generally well tolerated, with manageable toxicities. This review summarizes the profile of lenalidomide and the current evidence for its efficacy in multiple myeloma.

Angiogenesis Inhibitors↗

PubMed2005

Lenalidomide: an immunomodulatory drug.

Lenalidomide (CC-5013; Revlimid) represents one compound in a category of new medications known as immunomodulatory drugs. These compounds are thalidomide derivatives. Through relatively minor structural modifications, the potency of the medication is improved compared with the parent compound, and the side-effect profile has changed considerably. The neurologic toxicity and pro-thrombotic effects of thalidomide are reduced in the structural analog, although concerns regarding pro-thrombotic effects are still present when lenalidomide is combined with dexamethasone. Data supporting lenalidomide's use in myelodysplastic syndrome and multiple myeloma has been published over the past several years and presented at the May 2005 meeting of the American Society of Clinical Oncology. Further trials are ongoing for many other malignancies. This report will review the preclinical and clinical results of the investigations with this exciting new therapeutic, its toxicities and future prospects.

Animals↗

PubMed2006

Thalidomide and lenalidomide in the treatment of multiple myeloma.

Although multiple myeloma (MM) is incurable with currently available treatments, the introduction of thalidomide and the development of safer and more active thalidomide analogues represent a major advance in the therapy of this disease. Thalidomide, initially introduced for treatment of MM because of its anti-angiogenic properties, has shown remarkable activity alone and in combination with other drugs in patients across all stages of the disease. Given the potential for teratogenicity with thalidomide and the non-haematologic toxicities of the drug, several analogues referred to as "immunomodulatory drugs" (IMiDs) were developed with the intent of enhancing the immunomodulatory effect while minimizing the teratogenic risk. Lenalidomide (CC-5013) and Actimid (CC-4047) are the first such analogues to undergo clinical testing. Lenalidomide has shown impressive activity in relapsed refractory myeloma as well as newly diagnosed disease. The precise mechanism of anti-MM activity of thalidomide and the IMiDs is not clear, but studies suggest that several other mechanisms besides anti-angiogenic effects may play a role. In this paper we review the development, pharmacology, mechanism of action, pre-clinical and clinical efficacy, and the current status of thalidomide and the IMiDs in the treatment of MM.

Angiogenesis Inhibitors↗

PubMed2005

Recent clinical studies of the immunomodulatory drug (IMiD) lenalidomide.

Thalidomide is effective in the treatment of multiple myeloma. The immunomodulatory drug and thalidomide analogue lenalidomide is currently in late stage clinical development for MDS and multiple myeloma. This minireview highlights the course of initial and ongoing lenalidomide clinical development in oncology with reference to earlier thalidomide studies.

Clinical Trials as Topic↗

PubMed2005

Lenalidomide and thalidomide: mechanisms of action--similarities and differences.

Multiple myeloma is a B-cell malignancy characterized by an excess of monotypic plasma cells in the bone marrow. The molecular mechanisms that are involved in disease progression depend on the interaction between the multiple myeloma cells and the bone microenvironment. Because these mechanisms have been well characterized, it is possible to develop regimens that are more specific to pathways involved in the pathogenesis of multiple myeloma than is typical for conventional chemotherapy in disease management. Thalidomide and immunomodulatory drugs (IMiDs) have now been shown to block several pathways important for disease progression in multiple myeloma. First established as agents with antiangiogenic properties, thalidomide and IMiDs inhibit the production of interleukin (IL)-6, which is a growth factor for the proliferation of myeloma cells. In addition, they activate apoptotic pathways through caspase 8-mediated cell death. At the mitochondrial level, they are responsible for c-jun terminal kinase (JNK)-dependent release of cytochrome-c and Smac into the cytosol of cells, where they regulate the activity of molecules that affect apoptosis. By activating T cells to produce IL-2, thalidomide and IMiDs alter natural killer (NK) cell numbers and function, thus augmenting the activity of NK-dependent cytotoxicity. Data delineating these events have been derived from experiments done in resistant and sensitive multiple myeloma cell lines. Although thalidomide and IMiDs demonstrate similar biologic activities, IMiDs are more potent than thalidomide and achieve responses at lower doses. Lenalidomide, a thalidomide derivative, has also been shown to have a different toxicity profile. Our understanding of the mechanism of action of these agents has provided a platform for exciting clinical trials evaluating combinations of thalidomide and lenalidomide with both conventional chemotherapy and newer targeted agents.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma.

We report the results of a phase 2 trial using lenalidomide plus dexamethasone (Rev/Dex) as initial therapy for myeloma. Thirty-four patients were enrolled. Lenalidomide was given orally 25 mg daily on days 1 to 21 of a 28-day cycle. Dexamethasone was given orally 40 mg daily on days 1 to 4, 9 to 12, and 17 to 20 of each cycle. Objective response was defined as a decrease in serum monoclonal protein level by 50% or greater and a decrease in urine M protein level by at least 90% or to a level less than 200 mg/24 hours, confirmed by 2 consecutive determinations at least 4 weeks apart. Thirty-one of 34 patients achieved an objective response, including 2 (6%) achieving complete response (CR) and 11 (32%) meeting criteria for both very good partial response and near complete response, resulting in an overall objective response rate of 91%. Of the 3 remaining patients not achieving an objective response, 2 had minor response (MR) and one had stable disease. Forty-seven percent of patients experienced grade III or higher nonhematologic toxicity, most commonly fatigue (15%), muscle weakness (6%), anxiety (6%), pneumonitis (6%), and rash (6%). Rev/Dex is a highly active regimen with manageable side effects in the treatment of newly diagnosed myeloma.

Adult↗

PubMed2006

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma.

BACKGROUND: Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open-label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity. METHODS: Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints. RESULTS: In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression-free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow-up for those 11 patients was 13.5 months (range, 8.3-17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%). CONCLUSIONS: LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC.

Administration, Oral↗

PubMed2006

Efficacy of conventional cytogenetics and FISH for EGR1 to detect deletion 5q in hematological disorders and to assess response to treatment with Lenalidomide.

In clinical practice, whether FISH for EGR1 in interphase nuclei has similar efficacy to detect deletion 5q anomalies as conventional cytogenetic studies is unknown. We compared conventional cytogenetics and FISH for 145 patients with deletion 5q and detected this anomaly by both methods in 144. Nine patients with myelodysplasia were studied before and after treatment with Lenalidomide and results were concordant for 28 of 29 specimens. FISH did not detect anomalies other than deletion 5q in 31 patients. This study suggests FISH is useful to detect deletion 5q, but is not a substitute for conventional cytogenetics.

Adult↗

PubMed2006

Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications.

Natural killer T (NKT) cells are CD1d-restricted glycolipid reactive innate lymphocytes that play an important role in protection from pathogens and tumors. Pharmacologic approaches to enhance NKT cell function will facilitate specific NKT targeting in the clinic. Here we show that lenalidomide (LEN), a novel thalidomide (Thal) analog, enhances antigen-specific expansion of NKT cells in response to the NKT ligand alpha-galactosylceramide (alpha-GalCer) in both healthy donors and patients with myeloma. NKT cells activated in the presence of LEN have greater ability to secrete interferon-gamma. Antigen-dependent activation of NKT cells was greater in the presence of dexamethasone (DEX) plus LEN than with DEX alone. Therapy with LEN/Thal also led to an increase in NKT cells in vivo in patients with myeloma and del5q myelodysplastic syndrome. Together these data demonstrate that LEN and its analogues enhance CD1d-mediated presentation of glycolipid antigens and support combining these agents with NKT targeted approaches for protection against tumors.

Antigen Presentation↗

PubMed2026

RENOIR phase 3 rituximab-lenalidomide vs rituximab as maintenance treatment in relapsed/refractory follicular lymphoma.

Maintenance treatment in older patients with relapsed or refractory (R/R) follicular lymphoma (FL) remains an area of investigation. RENOIR was a multicenter, phase 3, open-label randomized trial conducted by the Fondazione Italiana Linfomi (FIL) in older patients with R/R FL after 1 or 2 previous therapies. Patients achieving partial response or complete response (CR) after 4 to 6 cycles of standard rituximab (R)-based chemotherapy were randomized 1:1 to maintenance with R alone (standard arm) or R plus lenalidomide (R2; experimental arm). The primary end point was 2-year progression-free survival (PFS) from randomization, with an expected hazard ratio (HR) of 0.5. A total of 152 patients (median age, 71 years) were enrolled. After induction, 129 (85%) achieved an overall response (CR, 58%) and were randomized to R (n = 65) or R2 (n = 64). At a median follow-up of 68 months, the 2-year PFS was 73% in the R2 arm and 64% in the R arm. An unplanned hypothesis-generating subgroup analysis showed a greater 2-year PFS benefit with R2 in patients aged <70 years: R2, 96% vs R, 69%. Two-year overall survival rates were similar (R2, 80% vs R, 89%). Grade 3/4 adverse events were more frequent in R2, mainly neutropenia and gastrointestinal disorders. In conclusion, the primary end point of the study was not met, and R2 maintenance did not significantly improve 2-year PFS in older patients with R/R FL, although a numerical benefit was observed. R2 showed a more favorable benefit-risk profile in patients aged <70 years, whereas in older patients careful consideration of individual tolerability is warranted. This trial was registered at www.clinicaltrials.gov as NCT02390869.

Humans↗

PubMed2005

Lenalidomide (Revlimid, CC-5013) in myelodysplastic syndromes: is it any good?

The myelodysplastic syndromes (MDS) can be divided into "early" and "advanced" disease by evaluation of prognostic variables such as the number of cytopenias, karyotype, and percentage of myeloblasts. Patients with an isolated interstitial deletion of chromosome 5q31 represent a distinct subset who may derive particular benefit from immunomodulatory drugs. Goals of therapy for early MDS focus on hematologic improvement and maximizing quality of life. Thalidomide, the prototype of the immunomodulatory drugs, yields major erythroid responses in some patients with early MDS, but dose-limiting neurologic toxicities limit its potential clinical benefit. Lenalidomide, a more potent and non-neurotoxic derivative, has shown promising results in early MDS, yielding hematologic improvement in almost half of patients, and transfusion independence with cytogenetic remissions in approximately two thirds of patients harboring the chromosome 5q31 deletion.

Aged↗

PubMed2026

Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial.

Teclistamab, a B cell maturation antigen-targeting bispecific antibody, has demonstrated substantial activity in relapsed multiple myeloma (MM), particularly in earlier lines of therapy, and may have higher efficacy in high-risk smoldering MM (HR-SMM) with a more functional immune system. In the randomized phase 2 ImmunoPRISM trial, we compared fixed-duration teclistamab with lenalidomide-dexamethasone (Rd) in HR-SMM. After a six-patient safety run-in, patients were randomized 2:1 to teclistamab or Rd. The primary endpoint was complete response (CR) rate. As of 26 May 2026, 59 patients were treated-45 received teclistamab and 14 received Rd. Teclistamab treatment induced a CR in 77.8% patients versus 0% with Rd, and minimal residual disease negativity at 10-5 in 82.2% patients. At a median follow-up of 24.5 months, 2-year progression-free survival was 92% with teclistamab versus 49% with Rd. Overall, response rates, duration of response and time to progression (TTP) were significantly improved in teclistamab compared to Rd. Toxicities in the teclistamab arm included grades 1-2 cytokine release syndrome, no neurotoxicity and no increase in grade 3 infections compared to Rd (20% versus 21%). No deaths occurred in either arm. Teclistamab represents a highly active immune-interception strategy for HR-SMM. ClinicalTrials.gov registration: NCT05469893 .

Journal Article↗