Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma

Richardson, Paul G.; Schlossman, Robert; Weller, Edie; Hideshima, Teru; Mitsiades, Constantine S.; Davies, Faith E.; LeBlanc, Richard; Catley, Laurence; Doss, Deborah; Kelly, Kathleen; McKenney, Mary; Mechlowicz, Julie; Freeman, Andrea; Deocampo, Reggie; Rich, Rebecca; Ryoo, Jean J.; Chauhan, Dharminder; Balinski, Kathe; Zeldis, Jerome B.; Anderson, Kenneth C.

doi:10.1182/blood-2002-03-0996

Cited by 750 publications

(484 citation statements)

References 19 publications

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“…However, reversible cytopenias were observed during the second cycle of treatment in subjects who received 25 mg ⁄ day. In the first study of the 24 evaluable patients treated according to this schedule, 29% had an M paraprotein reduction superior to 50%; in 71% of patients, the M component decreased to at least 25% (26). In the second study, 20% of the subjects achieved a reduction of M paraprotein superior to 50% at doses of 25-50 mg ⁄ day (27).…”

Section: Therapeutic Trialsmentioning

confidence: 99%

Lenalidomide in the treatment of multiple myeloma: a review

2008

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Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined antiinflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide.

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Section: Therapeutic Trialsmentioning

confidence: 99%

Lenalidomide in the treatment of multiple myeloma: a review

2008

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“…With its activity as a single agent or in combination, 11,15,[18][19][20][35][36][37][38] lenalidomide appears to be a strong candidate for inclusion in initial therapy of patients with aggressive Bcell non-Hodgkin's lymphoma. Furthermore, a recent study suggests that lenalidomide has improved activity in activated B-cell-like DLBCL compared with germinal center B-cell-like DLBCL.…”

Section: Ae N (%) Grade 1 Grade 2 Grade 3 Gradementioning

confidence: 99%

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi

et al. 2013

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“…Lenalidomide (Revlimid ® ) is a novel immunomodulatory agent that is more potent than thalidomide, 25 and has shown activity both preclinically 25 and clinically 34 against multiple myeloma. This drug seems also to add to the efficacy of steroids in these model systems 25,35 and to have a more favorable toxicity profile than thalidomide.…”

Section: R-mpmentioning

confidence: 99%

Initial Therapy of Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

Orłowski¹

2006

Hematology

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Multiple myeloma patients deemed to not be candidates for high-dose therapy followed by stem cell rescue who nonetheless need chemotherapy have traditionally received an oral regimen combining melphalan and prednisone. With the advent of novel agents, however, such as immunomodulatory drugs and proteasome inhibitors that are active in the relapsed/refractory setting, there has been an impetus to incorporate these new options into front-line therapy. Several phase II studies have recently revealed that addition of either thalidomide, lenalidomide, or bortezomib to melphalan and prednisone increased the overall and complete response rates, albeit at the cost of some increased toxicity. Randomized phase III studies of melphalan and prednisone with thalidomide have already shown that, compared to melphalan and prednisone alone, the three-drug regimen prolonged time to progression and overall survival in this population, thereby defining a new standard of care. Moreover, our increasing knowledge of the molecular role that cytogenetic abnormalities play in the biology of multiple myeloma and our growing chemotherapeutic armamentarium are beginning to allow us to rationally select therapies based on these characteristics of each patient's disease. Such a risk-and molecular-adapted strategy to the therapy of multiple myeloma promises to revolutionize and personalize our care of these patients and bring us closer to a cure for this disease.Using the diagnostic criteria recommended by the International Working Group, patients with multiple myeloma are classified as having either asymptomatic or symptomatic (Table 1) disease. 1 The latter population, generally considered candidates for a chemotherapy-based intervention, are then further divided into those who either are or are not eligible for high-dose chemotherapy followed by stem cell rescue. 2 Criteria that are weighed to help make this second distinction have generally included age, performance status, and co-morbid medical conditions. 2 There is some variability in these parameters and how they are applied, since studies examining stem cell transplantation have used different criteria. In regard to age, for example, which is the most objective of these measures, initial studies tended to enroll patients younger than 65 years of age, 3 while more recent studies suggest that transplant is safe in at least some who are over the age of 70 (for example 4,5 ). On the other hand, data suggesting that patients with poor-risk chromosomal features have a short time to progression after autologous transplantation have led to suggestions that even younger patients with these abnormalities may not be candidates for standard approaches. Nonetheless, as little as two years ago, there was general agreement that the standard of care for patients who were not eligible for transplantation and yet needed chemotherapy was melphalan

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Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma

Cited by 750 publications

References 19 publications

Lenalidomide in the treatment of multiple myeloma: a review

Lenalidomide in the treatment of multiple myeloma: a review

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi

Initial Therapy of Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

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