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At least 19 recordsLinked to original sources

PubMed2006

Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma.

OBJECTIVES: To examine dermatologic adverse effects of lenalidomide in patients with amyloidosis and multiple myeloma and to determine whether the adverse effects are different when lenalidomide is used alone compared with when it is used in combination with dexamethasone. DESIGN: Retrospective review of medical records. SETTING: Tertiary referral center. PATIENTS: Seventy-five patients with multiple myeloma and 23 patients with amyloidosis participating in clinical trials. INTERVENTION: In the 75 patients with multiple myeloma, lenalidomide was the treatment in 24 and lenalidomide and dexamethasone in 51. In the 23 patients with amyloidosis, lenalidomide was used alone. MAIN OUTCOME MEASURES: The frequency, type, severity, and time of onset of all skin eruptions that were temporally related to lenalidomide treatment were recorded. RESULTS: In the patients with amyloidosis treated with lenalidomide, 10 (43%) had rashes. In the patients with multiple myeloma, rashes occurred in 7 (29%) of those receiving lenalidomide alone and in 15 (29%) of those receiving lenalidomide and dexamethasone. The rashes were characterized as morbilliform, urticarial, dermatitic, acneiform, and undefined. Severe rashes required permanent discontinuation of lenalidomide therapy in 2 patients. In 23 patients (72%), rashes occurred in the first month after therapy was initiated; however, delayed-onset rashes occurred in 9 (28%). CONCLUSIONS: The prevalence of dermatologic adverse effects in patients receiving lenalidomide was higher in those with amyloidosis than in those with multiple myeloma. The prevalence of skin eruptions was not diminished by the concurrent use of systemic corticosteroids. Most skin eruptions were mild and did not necessitate withdrawal of lenalidomide therapy.

Amyloidosis↗

PubMed2005

Management of the relapsed/refractory myeloma patient: strategies incorporating lenalidomide.

The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide were limited to myelosuppression and a response rate of 72% was seen in relapsed/refractory patients. Three phase II studies subsequently evaluated the efficacy of single-agent lenalidomide or lenalidomide in combination with dexamethasone. As a single agent for post-transplant salvage therapy, lenalidomide 25 mg every 3 weeks has shown response rates as high as 44%. For patients with relapsed/refractory multiple myeloma, the MM-007 study has shown that lenalidomide alone or in combination with dexamethasone provides response rates between 37% and 41%. In MM-007, median progression-free survival was 5.5 months at early analysis and the median overall survival has yet to be reached. Preliminary data for the single-arm, multicenter, open-label MM-014 study showed that median time to progression was 5.6 months. Response rates indicate that 70% of patients had stable disease or better as the best response to treatment. Two randomized, phase III trials (MM-009 and MM-010) evaluated lenalidomide with high-dose dexamethasone versus high-dose dexamethasone alone for the treatment of relapsed/refractory multiple myeloma. Both MM-009 and MM-010 provided remarkably similar response rates for patients receiving lenalidomide and dexamethasone. In both trials response rates with the combination were greater than twice the response rates seen with high-dose dexamethasone alone. Indeed, an independent Data Monitoring Committee determined that both trials exceeded the prespecified efficacy value of P<.0015, recommending that the trials be discontinued and that lenalidomide be offered to patients on the dexamethasone arm of the trial if clinically indicated. Toxicities observed in studies of lenalidomide alone were low; the incidence of peripheral neuropathy was significantly lower than those noted in trials using thalidomide. Thrombocytopenia was a significant grade 3 or 4 toxicity observed; however, it was manageable with dose reduction. In contrast with high-dose dexamethasone, deep vein thrombosis has emerged as an important toxicity. Lenalidomide is currently being tested in combination with both standard and novel agents, including bortezomib, for patients with relapsed/refractory multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: clinical implications.

SGN-40, a humanized immoglobulin G1 (IgG1) anti-CD40 monoclonal antibody, mediates cytotoxicity against human multiple myeloma (MM) cells via suppression of interleukin (IL)-6-induced proliferative and antiapoptotic effects as well as antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we studied the clinical significance of an immunomodulatory drug lenalidomide on SGN-40-induced cytotoxicity against CD138(+)CD40(+) MM lines and patient MM cells. Pretreatment with lenalidomide sensitized MM cells to SGN-40-induced cell death. Combined lenalidomide and SGN-40 significantly induced MM apoptosis, evidenced by enhanced cleavage of caspase-3/8/poly(ADP-ribose)polymerase and increased sub-G(0) cells, compared with either single agent at the same doses. Pretreatment of effector cells with lenalidomide augmented SGN-40-induced MM cell lysis, associated with an increased number of CD56(+)CD3(-) natural killer (NK) cells expressing CD16 and LFA-1. Importantly, pretreatment with lenalidomide or lenalidomide and SGN-40 markedly enhanced NK-cell-mediated lysis of autologous patient MM cells triggered by SGN-40. Lenalidomide also up-regulated CD40L on CD56(+)CD3(-) NK cells, facilitating IL-2-mediated activation of NK cells. In addition, lenalidomide induced the CD56(dim) NK subset, which are more potent mediators of ADCC against target MM cells than the CD56(bright) NK subset. Finally, pretreatment of both effector and target MM cells with lenalidomide markedly enhanced SGN-40-mediated ADCC against CD40-expressing MM cells. These studies, therefore, show that the addition of lenalidomide to SGN-40 enhances cytotoxicity against MM cells, providing the framework for combined lenalidomide and SGN-40 in a new treatment paradigm to both target MM cells directly and induce immune effectors against MM.

Antibodies, Monoclonal↗

PubMed2005

Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro.

The thalidomide analogue and immunomodulatory drug (IMiD) lenalidomide (CC-5013, REVLIMID) is emerging as a useful treatment for a number of cancers and has recently entered phase III trials for multiple myeloma. It has been suggested that the anti-tumor effect of lenalidomide is related to its anti-angiogenic potency. In this regard, we have previously shown that lenalidomide inhibits angiogenesis in both rat and human in vitro models but does not affect endothelial cell proliferation. We now show that oral administration of lenalidomide attenuates growth factor-induced angiogenesis in vivo; the rat mesenteric window assay was utilized to show that lenalidomide significantly inhibits vascularization in a dose-dependent manner. We also found that lenalidomide significantly inhibits growth factor-induced endothelial cell migration. This correlates with the inhibitory effect of lenalidomide on growth factor-induced Akt phosphorylation, thereby providing a potential mechanism for its anti-migratory and subsequent anti-angiogenic effects. These data further support the use of lenalidomide as an orally administered drug for the effective treatment of angiogenesis-dependent conditions, including cancer, and suggest a potential mechanism of action.

Administration, Oral↗

PubMed2006

Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly.

Lenalidomide (Revlimid, CC-5013) belongs to a line of compounds known as immunomodulatory drugs (IMiDs) that are under clinical investigation in hematopoietic and solid tumor cancers. Lenalidomide efficacy has been reported in clinical trials of multiple myeloma and myelodysplastic syndromes (MDS), particularly in MDS patients with a del 5q cytogenetic abnormality, with or without other cytogenetic abnormalities. Here we report that lenalidomide inhibits proliferation of chromosome 5 deleted hematopoietic tumor cell lines in vitro, whether from the B cell, T cell, or myeloid lineage. There was diversity in the responses of the various cell lines to lenalidomide, with one undergoing cell cycle arrest, and others undergoing apoptosis. In the most lenalidomide-sensitive chromosome 5 deleted cell line, Namalwa CSN.70, the compound induced G0/G1 cell cycle arrest, inhibited Akt and Gab1 phosphorylation, and inhibited the ability of Gab1 to associate with a receptor tyrosine kinase. Lenalidomide also enhanced AP-1 transcriptional activity in Namalwa, but not in the other cell lines tested. These studies provide evidence for the mechanism of action of lenalidomide in chromosome 5 deleted hematopoietic tumors in vitro, and may provide a better understanding of the drug's activity in clinical applications.

Adaptor Protein Complex 1↗

PubMed2006

Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy.

BACKGROUND: Lenalidomide is active and well tolerated in relapsed and refractory multiple myeloma. We conducted a phase I/II trial of the combination of lenalidomide and chemotherapy to evaluate the safety and efficacy of the combination. METHODS: The 62 patients enrolled received liposomal doxorubicin 40 mg/m(2) i.v. and vincristine 2 mg i.v. on day 1, dexamethasone 40 mg p.o. on days 1-4 (DVd), and lenalidomide on days 1-21 in 28-day cycles. Primary end points were maximum tolerated dose (MTD) of lenalidomide with DVd chemotherapy and overall response rate (ORR) by Southwest Oncology Group criteria of the combination. FINDINGS: The median age was 62 years, 70% of patients were males and 65% had refractory multiple myeloma. The MTD of lenalidomide with DVd chemotherapy was 10 mg and the dose-limiting toxicity was non-neutropenic sepsis. After 7.5 months of median follow-up, the ORR of the combination was 75%, with 29% of patients achieving a complete or near complete remission. The median progression-free survival was 12 months, while the median overall survival has not yet been reached. INTERPRETATION: The combination of lenalidomide and DVd chemotherapy was well tolerated and resulted in high response rates in this mostly refractory patient population. Evaluation of this combination in newly diagnosed patients is warranted.

Aged↗

PubMed2006

A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma.

This multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21 days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first 70 patients showed increased grade 3/4 myelo-suppression in patients receiving 15 mg twice daily (41% versus 13%, P = .03). An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25% (24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups was 28 and 27 months, respectively. Median progression-free survival was 7.7 months on once-daily versus 3.9 months on twice-daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically significant grade 3/4 myelosuppression was shorter in the twice-daily group (1.8 vs 5.5 months, P = .05). Significant peripheral neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone.

Adult↗

PubMed2026

IDH2 clonal hematopoiesis and IKAROS loss cooperate in a B-ALL subtype after lenalidomide therapy for multiple myeloma.

Lenalidomide, a maintenance treatment in multiple myeloma first-line therapy, increases the risk of secondary malignancies, including B-cell precursor acute lymphoblastic leukemia (B-ALL). We present a comprehensive molecular characterization of 57 patients with lenalidomide-associated B-ALL (LenB-ALL), revealing 3 mutational subgroups: (1) TP53mt (30%); (2) IDH2mt (p.R140Q) (23%); and (3) other, including NRAS/KRASmt. Remarkably, IDH2 R140Q mutations were highly enriched in LenB-ALL compared with those in primary B-ALL (P< .001). Furthermore, IKZF1 intragenic deletions, often subclonal and likely RAG recombinase-mediated, were observed in 54% (7/13) of IDH2mt patients with LenB-ALL. IDH2 mutations were not restricted to the leukemic clone: they persisted during measurable residual disease-negative remission and were identified in lymphoid as well as myeloid cell populations using fluorescence-activated cell sorting and single-cell RNA sequencing. This indicates a preleukemic origin of the IDH2 mutation within the context of clonal hematopoiesis. Transcriptomic and DNA methylation analyses revealed a distinct gene expression profile and a DNA hypermethylation phenotype in IDH2mt LenB-ALL, including IDH2mt-specific as well as lenalidomide-associated features. We propose that lenalidomide promotes the expansion of IDH2-mutated clonal hematopoiesis and, via IKAROS downregulation, induces a maturation arrest at the B-cell precursor stage. Subsequent genetic or epigenetic alterations render leukemogenesis independent of ongoing lenalidomide exposure. All these data define IDH2mt B-ALL as a distinct molecular subtype that is markedly overrepresented after lenalidomide treatment and highlight clonal hematopoiesis as a key contributing factor in the development of LenB-ALL.

Humans↗

PubMed2006

Lenalidomide in the context of complex karyotype or interrupted treatment: case reviews of del(5q)MDS patients with unexpected responses.

Lenalidomide has particular activity in patients with transfusion-dependent del(5q) myelodysplastic syndromes (MDS), but mechanistic information is limited regarding the relationship between erythroid and cytogenetic responses. We reviewed medical records from three distinct subgroups of del(5q) MDS patients who had unexpected effects with lenalidomide treatment: 1. two patients with complex karyotypes who achieved both cytogenetic remissions and transfusion independence; 2. two patients with 5q- syndrome who took lenalidomide for less than 12 weeks but remained transfusion independent for 15+ months still displaying del(5q) metaphases after 6 and 12 months; and 3. one patient who was a non-responder on lenalidomide during treatment but became transfusion independent for 13+ months after discontinuation. All but the latter patient in this series had reduction of affected metaphases, suggesting that erythroid responses might be mediated by result from partial or complete suppression of the malignant clone, either directly or indirectly through modulation of the bone marrow microenvironment. These clinical observations illustrate the heterogeneity of del(5q)MDS pathogenesis and the diversity of lenalidomide responses within this patient subset.

Adult↗

PubMed2006

Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors.

INTRODUCTION: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different toxicity profile. In preclinical trials it has shown synergy with chemotherapy. PATIENTS AND METHODS: Primary objective of this study was to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study design. Between September 2004 and May 2005, 14 patients with pathologically proven solid tumors, < or =2 prior chemotherapy regimens, performance status ECOG 0/1, and adequate organ function were enrolled. Dose limiting toxicities (DLT) were defined as > or = grade 3 non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1. RESULTS: Three of four patients treated at dose level 1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 10 mg orally daily on Days 1-14 of a 21 day cycle experienced DLT (grade 3 electrolyte changes in two patients, and grade 4 neutropenia in one patient). Ten patients were treated at dose level -1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 5 mg orally daily on Days 1-14 of a 21 day cycle with one DLT (Grade 4 neutropenia). There were no treatment-related deaths or irreversible toxicities. Of the 14 response-evaluable patients, five achieved a partial response (5 out of 9 patients with non-small cell lung cancer. CONCLUSIONS: Docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, with lenalidomide 5 mg orally daily on Days 1-14 days of a 21 day cycle is the maximum tolerated dose without the use of prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted.

Administration, Oral↗

PubMed2006

Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion.

BACKGROUND: Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31- clone in patients with this disorder. METHODS: One hundred forty-eight patients received 10 mg of lenalidomide for 21 days every 4 weeks or daily. Hematologic, bone marrow, and cytogenetic changes were assessed after 24 weeks of treatment by an intention-to-treat analysis. RESULTS: Among the 148 patients, 112 had a reduced need for transfusions (76%; 95% confidence interval [CI], 68 to 82) and 99 patients (67%; 95% CI, 59 to 74) no longer required transfusions, regardless of the karyotype complexity. The response to lenalidomide was rapid (median time to response, 4.6 weeks; range, 1 to 49) and sustained; the median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. The maximum hemoglobin concentration reached a median of 13.4 g per deciliter (range, 9.2 to 18.6), with a corresponding median rise of 5.4 g per deciliter (range, 1.1 to 11.4), as compared with the baseline nadir value before transfusion. Among 85 patients who could be evaluated, 62 had cytogenetic improvement, and 38 of the 62 had a complete cytogenetic remission. There was complete resolution of cytologic abnormalities in 38 of 106 patients whose serial bone marrow samples could be evaluated. Moderate-to-severe neutropenia (in 55% of patients) and thrombocytopenia (in 44%) were the most common reasons for interrupting treatment or adjusting the dose of lenalidomide. CONCLUSIONS: Lenalidomide can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients who have the myelodysplastic syndrome with the 5q31 deletion. (ClinicalTrials.gov number, NCT00065156 [ClinicalTrials.gov].).

Adult↗

PubMed2006

The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis.

Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, is highly active in patients with multiple myeloma. We studied the toxicity and efficacy of lenalidomide in patients with AL. Patients with symptomatic AL, a measurable plasma cell disorder, and adequate hematologic and renal reserve were eligible. Patients received single-agent lenalidomide. If there was no evidence of progression after 3 months or of hematologic response after 3 cycles, dexamethasone was added. Twenty-three patients were enrolled. Thirteen were previously treated. Organ involvement was cardiac (64%), renal (73%), hepatic (23%), and nerve (14%). Within the first 3 cycles of therapy, 10 patients discontinued treatment: 4 early deaths, 3 adverse events, and 3 other causes. With a median follow-up of 17 months, 10 patients responded to treatment. In these patients, responses included 9 hematologic, 4 renal, 2 cardiac, and 2 hepatic. All but one of the responders had dexamethasone added to their treatment program. The most common grade 3 or 4 adverse events at least possibly attributable to lenalidomide were neutropenia (45%), thrombocytopenia (27%), rash (18%), and fatigue (18%). In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation.

Administration, Oral↗

PubMed2007

Risk of thrombosis with lenalidomide and its prevention with aspirin.

Lenalidomide, an analog of thalidomide, is an effective new treatment for multiple myeloma. Both compounds are associated with an increased risk of venous thromboembolism, particularly when used in combination with high-dose dexamethasone. As new trials with lenalidomide are being planned and performed, investigators are placing high importance on reducing the risk of thrombosis by incorporating an antithrombotic agent into the therapeutic regimen. Low-molecular-weight heparin, warfarin, and aspirin have all been suggested as candidate drugs for thromboprophylaxis, but none of these agents have been evaluated in randomized clinical trials. A body of opinion has evolved that aspirin is very effective in preventing venous thrombosis in myeloma patients treated with lenalidomide. If correct, this view has important implications, because aspirin is inexpensive and is safer and more convenient than anticoagulants. On the other hand, aspirin is less effective than anticoagulants for preventing venous thrombosis in other high-risk groups, and therefore might not be the most appropriate choice for preventing of venous thrombosis in myeloma patients. This commentary examines the strength of the evidence supporting the effectiveness of aspirin in preventing venous thrombosis in multiple myeloma patients treated with lenalidomide. It is concluded that the evidence that aspirin is efficacious in preventing venous thrombosis in myeloma patients is based on "before/after" and retrospective studies, with potential for bias and confounders. There is, therefore, a critical need to incorporate a randomized comparison of aspirin with an anticoagulant in future trials evaluating lenalidomide in multiple myeloma.

Anticoagulants↗

PubMed2006

Current therapeutic uses of lenalidomide in multiple myeloma.

Thalidomide has demonstrated a broad spectrum of pharmacological and immunological effects, with potential therapeutic applications that span a wide spectrum of diseases: cancer and related conditions; infectious diseases; autoimmune diseases; dermatological diseases; and other disorders such as sarcoidosis, macular degeneration and diabetic retinopathy. Immunomodulatory derivative lenalidomide has more potent antitumour and anti-inflammatory effects. The molecular mechanisms of antitumour activity of lenalidomide have been extensively studied in multiple myeloma (MM). It directly induces growth arrest and/or apoptosis of even drug-resistant MM cells; inhibits binding of MM cells to bone marrow extracellular matrix proteins and stromal cells; modulates cytokine secretion and inhibits angiogenesis in the bone marrow milieu; and augments host antitumour immunity. Importantly, lenalidomide induces significant clinical responses even in patients with relapsed/refractory MM. Therefore, lenalidomide represents a new class of antitumour agents that is useful in the treatment of MM. Lenalidomide has received fast track designation from the FDA for the treatment of MM and myelodysplastic syndromes.

Animals↗

PubMed2006

Thalidomide and lenalidomide in multiple myeloma.

Multiple myeloma is a treatable but not necessarily a curable plasma-cell cancer. After decades of minimal progress, two new classes of drugs with novel mechanisms of action - immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib) - have been introduced for the treatment of this disease. Thalidomide and lenalidomide have shown great activity as single agents and in combination with glucocorticoids for the treatment of chemotherapy-refractory myeloma. Thalidomide - and more recently lenalidomide - in combination with dexamethasone have shown promising results as induction therapy. These drugs can easily be combined with other chemotherapeutic agents to potentiate the anti-myeloma effect. The immunomodulatory function of these drugs can be successfully exploited to control residual disease during remission. Thus, both thalidomide and lenalidomide have ushered in a new era of optimism in the management of this incurable cancer.

Humans↗

PubMed2005

Lenalidomide: patient management strategies.

Experience with thalidomide has underscored the need for diligent monitoring and management of side effects to achieve optimal therapeutic benefit. Initial phase II and III results with lenalidomide, a thalidomide analogue, have confirmed impressive response rates with a significantly more favorable toxicity profile. The Cleveland Clinic experience with lenalidomide alone or in combination with pegylated liposomal doxorubicin, vincristine, and reduced schedule dexamethasone will be described. Peripheral neuropathy and deep venous thrombosis (DVT). Low-dose aspirin alleviated DVT when lenalidomide was used in combination with anthracycline-containing chemotherapy. Strategies for managing these toxicities and for recognition and management of lenalidomide-associated myelosuppression are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial.

In immunoglobulin light chain (AL) amyloidosis, amyloid fibril deposits derived from immunoglobulin light chains produced by a clonal plasma cell dyscrasia accumulate in tissues and damage vital organs. Treatment regimens used in multiple myeloma can be effective in AL amyloidosis; however, patients with this disease often tolerate these regimens poorly because of multisystem organ dysfunction. Thalidomide and lenalidomide have both been shown to be effective in myeloma. In this report, we describe results of a phase 2 trial of the use of lenalidomide, as a single agent and in combination with dexamethasone, for the treatment of AL amyloidosis. Thirty-four patients with AL amyloidosis, most with prior therapies, were enrolled in the trial. The initial dose of lenalidomide used (25 mg/d) was poorly tolerated; however, a reduced dose of 15 mg/d was generally well tolerated. Of 24 evaluable patients, 7 (29%) achieved a hematologic complete response and 9 (38%) achieved a partial hematologic response, for an overall hematologic response rate of 67%. Hematologic responses were also associated with clinical responses. Fatigue and myelosuppression were the most common treatment-related adverse events (35%), while thromboembolic complications (9%) were the most serious. Findings from this trial indicate that lenalidomide can be effective in treating AL amyloidosis.

Adult↗

PubMed2006

Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study.

PURPOSE: Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) have profound immune defects and limited treatment options. Given the dramatic activity of lenalidomide in other B-cell malignancies and its pleotropic immunomodulatory effects, we conducted a phase II trial of this agent in CLL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell CLL (B-CLL) were eligible if they required treatment as per the National Cancer Institute Working Group 1996 guidelines. Lenalidomide was administered orally at 25 mg on days 1 through 21 of a 28-day cycle. Response was assessed after each cycle. Patients were to continue treatment until disease progression, unacceptable toxicity, or complete remission. Rituximab was added to lenalidomide on disease progression. RESULTS: Forty-five patients were enrolled, with a median age of 64 years. Sixty-four percent of the patients had Rai stage III or IV disease, and 51% were refractory to fludarabine. The overall response rate was 47%, with 9% of the patients attaining a complete remission. Fatigue, thrombocytopenia, and neutropenia were the most common adverse effects noted in 83%, 78%, and 78% of the patients, respectively. CONCLUSION: Lenalidomide is clinically active in patients with relapsed or refractory B-CLL. These findings are encouraging and warrant further investigation of this agent in the treatment of this disorder.

Adult↗