Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma.
ABSTRACT To determine the long-term effects of a combined regimen of lenalidomide and dexamethasone (Rev-Dex) on time to progression, progression-free survival, and overall survival (OS) in patients with multiple myeloma.
From March 2004 through October 2004, 34 patients were registered for the study. They were treated with 25 mg/d of lenalidomide on days 1 through 21 of a 28-day cycle and 40 mg/d of dexamethasone on days 1 through 4, 9 through 12, and 17 through 20 of each cycle. After 4 cycles of therapy, patients were allowed to discontinue treatment to pursue autologous stem cell transplant (SCT). Treatment beyond 4 cycles was permitted at the physician s discretion.
Thirteen patients proceeded to SCT after initial therapy and were censored at that time point for purposes of calculation of response. Thirty-one patients achieved an objective response, defined as a partial response or better (91%; 95% confidence interval, 79%-98%), with a complete response plus very good partial response rate of 56%. The complete response plus very good partial response among the 21 patients who received Rev-Dex without SCT was 67%. The 2-year progression-free survival rates for patients proceeding to SCT and patients remaining on Rev-Dex were 83% and 59%, respectively; the OS rates were 92% and 90% at 2 years and 92% and 85% at 3 years, respectively. The 3-year OS rate for the whole cohort was 88%.
The Rev-Dex regimen is highly active in the treatment of newly diagnosed multiple myeloma. Responses are durable with a low progression rate at 2 years. Randomized trials that incorporate quality-of-life measures are needed to determine if this and other combination regimens are better used early in therapy or should be reserved for later interventions.
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ABSTRACT: Lenalidomide is a more potent and better tolerated immunomodulatory drug (IMiD) as compared to thalidomide, the first-in-class IMiD. The mechanism of action of lenalidomide in multiple myeloma (MM) includes direct antitumor, immunomodulatory, and regulatory effects on the plasma cell-bone marrow niche interaction. Lenalidomide in combination with dexamethasone has shown a significantly higher efficacy as compared to dexamethasone alone in the treatment of relapsed or refractory MM in terms of overall response (OR) rate, complete response (CR) rate, time to progression (TTP), and overall survival (OS). Dosing, duration, and overall benefit of dexamethasone combination remains to be elucidated in ad-hoc trials, which may impact the tolerability and efficacy of the recommended schedule of lenalidomide rescue treatment. Depth of response achieved with lenalidomide and dexamethasone is associated with improvements in response duration, TTP, and OS, regardless of when the response is achieved. Although the probability of achieving a CR or very good partial response (VGPR) decreases over time, patients who are able to tolerate treatment in the absence of disease progression continue to experience benefits. However, optimal duration of rescue treatment from the time-point of best response has not been formally established. Recent data from phase 3 clinical trials also suggest the benefit of single-agent lenalidomide as maintenance after first-line treatment, and of lenalidomide combination therapy with conventional chemotherapy or new agents as induction treatment, in both autologous stem cell transplantation (ASCT) eligible and ineligible MM patients. Concerns about second primary neoplasms have been recently raised, and need further investigation. Taken together, these facts open new clinical settings in which lenalidomide therapy may benefit MM patients and deepen IMiD knowledge, especially in the continued rescue treatment and maintenance settings. Further study is warranted to optimize treatment with IMiDs.Advances in Therapy 12/2011; 28(8). DOI:10.1007/s12325-011-0076-3 · 2.44 Impact Factor
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ABSTRACT: Smoldering multiple myeloma (SMM) bridges the gap between monoclonal gammopathy of undetermined significance (MGUS) - a mostly pre-malignant disorder - and active multiple myeloma (MM). Until recently, no interventional study in patients with SMM showed improved overall survival with therapy as compared to observation. A report from the PETHEMA-GEM group described both fewer myeloma related events and better overall survival among patients with high-risk SMM patients who were treated with lenalidomide and dexamethasone. This unique study has prompted us to review current knowledge about SMM, and address the following questions: 1) are there patients currently defined as SMM, who should be treated routinely? 2) should the definitions of SMM and MM be reconsidered? 3) has the time come when not treating is more dangerous than treating; and 4) could unintended medical harm result from overzealous intervention? Our conclusion is that those patients with the highest risk SMM--extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging -- be reclassified as active MM, such that they can receive MM appropriate therapy and the paradigm of careful observation for patients with SMM can be preserved.Blood 10/2013; DOI:10.1182/blood-2013-08-520890 · 9.78 Impact Factor
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ABSTRACT: Lenalidomide was approved for the treatment of relapsed and refractory multiple myeloma (rrMM) based on MM009 and MM010 clinical trials. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 90 consecutive patients treated in our center with lenalidomide and dexamethasone (LenDex) between 2007 and 2012. The overall response rate to this treatment was 68 % and the median duration of response was 13.6 months. Patients treated in first relapse and those treated with LenDex longer than 1 year achieved the best responses. Cytogenetics was associated with PFS and best response to treatment was the only variable associated with longer PFS and OS in univariate and multivariate analyses. Our analysis confirmed that LenDex is effective in rrMM patient, well tolerated, and applicable to the majority of patients outside clinical trials; patients achieving a complete response, even in the context of relapse, have a longer survival; quality of response is better when lenalidomide is used in second line than later on and it is a good surrogate marker for OS. Accordingly, CR should be aimed in the rrMM setting, especially in fit patients. Previous treatment with thalidomide should not hamper the option for lenalidomide therapy.Annals of Hematology 07/2014; 94(1). DOI:10.1007/s00277-014-2164-3 · 2.40 Impact Factor