Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma

Centre René Gauducheau, Bd. Jacques Monod, Nantes, St. Herblain, France.
Haematologica (Impact Factor: 5.81). 05/2010; 95(10):1738-44. DOI: 10.3324/haematol.2009.015917
Source: PubMed


This retrospective pooled analysis of two phase III trials (MM-009/MM-010) compared clinical outcomes of patients who achieved a complete response or very good partial response to treatment with lenalidomide plus dexamethasone with the outcomes of those who only achieved a partial response.
Patients (n=353) received lenalidomide (25 mg/day for 21 days of each 28-day cycle) plus dexamethasone (40 mg on days 1-4, 9-12, and 17-20 for four cycles, and only on days 1-4 after the first four cycles). Time to response, duration of response, time-to-progression, overall survival, and adverse events were investigated for patients who had a complete or very good partial response and compared with those of patients who had a partial response.
At the time of unblinding, 32% of patients had achieved a complete or very good partial response and 28% had a partial response. Half (50.5%) of the patients who had a partial response as their initial response achieved a complete or very good partial response with further treatment. The probability of achieving a complete or very good partial response with continued lenalidomide treatment decreased with delayed achievement of a partial response (by cycle 4 versus later); however, it remained clinically significant. With an extended follow-up of 48 months, the median response duration, time-to-progression, and overall survival were longer in patients with a complete or very good partial response than in those with a partial response (24.0 versus 8.3 months, P<0.001; 27.7 versus 12.0 months, P<0.001; not reached versus 44.2 months, P=0.021, respectively). The benefit of a complete or very good partial response was independent of when it was achieved.
Continuing treatment with lenalidomide plus dexamethasone to achieve best response, in the absence of disease progression and toxicity, provided deeper remissions and greater clinical benefit over time for patients in this study.

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Available from: Robert Douglas Knight, Mar 26, 2014
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    • "The impact of the depth of response on survival in the relapse setting is still controversial. Based on recent evidence, complete response (CR) seems to be the only condition linked with long-term remission and prolonged survival, especially when supported by multi-parameter flow cytometry or molecular studies.10,11 Instead, near-CR, very good partial remission (VGPR) and partial remission (PR) all seem to have virtually identical outcomes.10,11 "
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    • "Several studies have shown the synergic activity of bortezomib with the alkylating agent melphalan whether in combination with prednisone in elderly patients or with dexamethasone in relapsed patients, observing a final response rate of about 70%, with a rate of high quality response (≥VGPR) ranging from 15 to 34% 7–9. Considering the importance of achieving a high-quality response 10–14 even beyond frontline setting 15,16, and the good safety profile observed for single agent fotemustine, we conducted a dose escalation clinical study to evaluate the tolerability and the activity of a combination therapy including fotemustine, bortezomib, and dexamethasone. "
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