Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232)

Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Blood (Impact Factor: 10.43). 09/2010; 116(26):5838-41. DOI: 10.1182/blood-2010-08-303487
Source: PubMed

ABSTRACT The Southwest Oncology Group conducted a randomized trial comparing lenalidomide (LEN) plus dexamethasone (DEX; n = 97) to placebo (PLC) plus DEX (n = 95) in newly diagnosed myeloma. Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 together with LEN 25 mg/day for 28 days or PLC. Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC. Crossover from PLC-DEX to LEN-DEX was encouraged on progression. One-year progression-free survival, overall response rate, and very good partial response rate were superior with LEN-DEX (78% vs 52%, P = .002; 78% vs 48%, P < .001; 63% vs 16%, P < .001), whereas 1-year overall survival was similar (94% vs 88%; P = .25). Toxicities were more pronounced with LEN-DEX (neutropenia grade 3 or 4: 21% vs 5%, P < .001; thromboembolic events despite aspirin prophylaxis: 23.5% [initial LEN-DEX or crossover] vs 5%; P < .001). This trial was registered at as #NCT00064038.

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    • "The results of these experiences are in favour of low dose of dexamethasone. Furthermore, clinical experience with lenalidomide indicates that early use in MM therapy is associated with a higher response rate and, possibly, prolonged survival [30]. To further improve the outcome of lenalidomide, combination regimens (BiRd, VRD, RAD, VDCR, and VRDD) [31] [32] [33] [34] [35] have been evaluated or are under investigation in both old and young MM patients, in transplant and non transplant settings. "
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    ABSTRACT: Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs) and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host's immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN) as a possible mediator of its therapeutical effects.
    Advances in Hematology 08/2012; 2012:842945. DOI:10.1155/2012/842945
  • Blood reviews 11/2010; 24 Suppl 1:S1-3. DOI:10.1016/S0268-960X(10)00069-X · 5.45 Impact Factor
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    ABSTRACT: DISEASE OVERVIEW: Multiple myeloma is malignant plasma-cell disorder that accounts for ∼10% of all hematologic malignancies. DIAGNOSIS: The diagnosis requires (1) 10% or more clonal plasma cells on bone marrow examination or a biopsy-proven plasmacytoma plus (2) evidence of end-organ damage felt to be related to the underlying plasma cell disorder. RISK STRATIFICATION: Patients with 17p deletion, t(4;14), t(14;16), t(14;20), and karyotypic deletion 13 or hypodiploidy are considered to have high-risk myeloma. All others are considered to have standard-risk disease. RISK-ADAPTED THERAPY: Standard-risk patients are treated with nonalkylator-based therapy such as lenalidomide plus low-dose dexamethasone (Rd) followed by autologous stem-cell transplantation (ASCT). If patients are tolerating the induction regimen treatment well, an alternative strategy is to continue initial therapy after stem-cell collection, reserving ASCT for first relapse. High-risk patients are treated with a bortezomib-based induction followed by ASCT and then bortezomib-based maintenance. Patients not eligible for ASCT can be treated with Rd for standard risk disease or a bortezomib-based regimen if high-risk features are present. To reduce toxicity, when using bortezomib, the once-weekly dose is preferred; similarly, when using dexamethasone, the low-dose approach (40 mg once a week) is preferred, unless there is a need for rapid disease control. MANAGEMENT OF REFRACTORY DISEASE: Patients with indolent relapse can be treated first with lenalidomide, bortezomib, or alkylators plus low-dose corticosteroids. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. The most promising new agents in development are pomalidomide and carfilizomib.
    American Journal of Hematology 01/2011; 86(1):57-65. DOI:10.1002/ajh.21913 · 3.48 Impact Factor

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