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: 10.45). 09/2010; 116(26):5838-41. DOI: 10.1182/blood-2010-08-303487
Source: PubMed


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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    • "In a randomised Southwest Oncology Group (SWOG) trial in newly diagnosed MM patients, including those over 65 years of age, lenalidomide in combination with dexamethasone (Len/Dex) proved to be better than dexamethasone plus placebo [123]. The dose of dexamethasone used in combination with lenalidomide is important with respect to the tolerability of the regimen, especially in elderly patients. "
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    ABSTRACT: Multiple myeloma is the second most frequent haematological disease. The introduction of high-dose melphalan followed by autologous haematopoietic cell transplant (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want to definitively cure the disease. Treatment goals for transplant-eligible and non-transplant-eligible patients should be to prolong survival by achieving the best possible response, while ensuring quality of life. The treatment should be individualized on the basis of host and disease features and better monitoring of the response upon use of high-sensitivity techniques for evaluating residual disease.
    Blood reviews 06/2015; 351. DOI:10.1016/j.blre.2015.06.001 · 5.57 Impact Factor
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    • "The number of participant drop-outs was acceptable (<20%) in the majority of the trials. Other biases that existed in the trials included: early stopping of lenalidomide maintenance therapy based on an increased incidence of adverse events [23], [25]; early trial unblinding and crossover [23], [24], [26], [27]; trial designed and data analyzed by the manufacturer of lenalidomide [21], [26]; and patients receiving inappropriate doses of steroid treatment [22]. "
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    ABSTRACT: In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a meta-analysis of RCTs examining the efficacy and safety of lenalidomide for MM. Databases were searched using the terms "lenalidomide or revlimid AND multiple myeloma."RCTs evaluating initial or maintenance therapeutic outcomes were included. Main outcome measures were response rates, progression-free survival (PFS), overall survival, and adverse events. Seven trials were included (N = 192-614 participants). Lenalidomide doses and treatment regimens differed between trials. Complete response (CR) and very good partial response (VGPR) risk ratios (RR) favored lenalidomide over placebo (CR = 2.54, 95% confidence interval [CI] = 1.29-5.02; VGPR = 2.82, 95% CI = 1.30-6.09). The PFS hazard ratio favored lenalidomide over placebo (0.37, 95% CI = 0.33-0.41). For adverse events, neutropenia, deep vein thrombosis (DVT), infection, and hematologic cancer RR favored placebo over lenalidomide (neutropenia: 4.74, 95% CI = 2.96-7.57; DVT: 2.52; 95% CI: 1.60-3.98; infection: 1.98; 95% CI: 1.50-2.62; hematologic cancer: 3.20; 95% CI: 1.28-7.98). Lenalidomide is an effective treatment for MM; however, treatment-related adverse events must be considered and appropriate adjustments and/or prophylactic treatment should be initiated where possible.
    PLoS ONE 05/2013; 8(5):e64354. DOI:10.1371/journal.pone.0064354 · 3.23 Impact Factor
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    • "The specificity of the antibody was determined by carrying out the competitive assay using dexamethasone that is administered in combined therapy with LND [38], as a competitor. It was found that dexamethasone does not show any immunoreactivity with the anti-LND antibody. "
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    ABSTRACT: Background For therapeutic monitoring and pharmacokinetic studies of lenalidomide (LND), the potent drug for treatment of multiple myeloma (MM), a specific antibody was required for the development of a sensitive immunoassay system for the accurate determination of LND in plasma. Results In this study, a hapten of LND (N-glutaryl-LND) was synthesized by introducing the glutaryl moiety, as a spacer, into the primary aromatic amine site of the LND molecular structure. The structure of the hapten (G-LND) was confirmed by mass, 1H-NMR, and 13C spectrometric techniques. G-LND was coupled to each of bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH) proteins by ethyl-3-(3-dimethylaminopropyl) carbodiimide as a coupling reagent. LND-KLH conjugate was used as an immunogen. Four female 2-3 months old New Zealand white rabbits were immunized with an emulsion of LND-KLH with Freund`s adjuvant. The immune response of the rabbits was monitored by direct enzyme-linked immunosorbent assay (ELISA) using LND-BSA immobilized onto microwell plates as a solid phase. The rabbit that showed the highest antibody titer and affinity to LND was scarified and its sera were collected. The IgG fraction was isolated and purified by affinity chromatography on protein A column. The specificity of the purified antibody for LND was evaluated by indirect competitive ELISA using dexamethasone as a competitor as it is used with LND in a combination therapy. Conclusions The high affinity of the antibody (IC50 = 10 ng/mL) will be useful in the development of an immunoassay system for the determination of plasma LND concentrations. Current research is going to optimize the assay conditions and validate the procedures for the routine application in clinical laboratories.
    Chemistry Central Journal 10/2012; 6(1):125. DOI:10.1186/1752-153X-6-125 · 2.19 Impact Factor
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