Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement.
ABSTRACT An expert panel convened to reach a consensus regarding the optimal use of lenalidomide in combination with dexamethasone (Len/Dex) in patients with relapsed or refractory multiple myeloma (RRMM). On the basis of the available evidence, the panel agreed that Len/Dex is a valid and effective treatment option for most patients with RRMM. As with other therapies, using Len/Dex at first relapse is more effective regarding response rate and durability than using it after multiple salvage therapies. Len/Dex may be beneficial regardless of patient age, disease stage and renal function, although the starting dose of lenalidomide should be adjusted for renal impairment and cytopenias. Long-term treatment until there is evidence of disease progression may be recommended at the best-tolerated doses of both lenalidomide and dexamethasone. Recommendations regarding the prevention and management of adverse events, particularly venous thromboembolism and myelosuppression, were provided on the basis of the available evidence and practical experience of panel members. Ongoing trials will provide more insight into the effects of continuous lenalidomide-based therapy in myeloma.
- JAMA The Journal of the American Medical Association 01/2007; 296(21):2558-60. · 29.98 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Total Therapy 1, the first tandem autotransplant trial for newly diagnosed patients with multiple myeloma, was designed to increase the frequency of complete response (CR) and thereby extend survival. With a median follow-up of 12 years, 62 of 231 initially enrolled patients are alive (17% at 15 years); 31 remain event free (7% at 15 years) including 16 of 94 (41%) that initially achieved CR. Currently alive patients less frequently had cytogenetic abnormalities (CAs) at baseline (P = 0.002), postenrolment (P < 0.001) and at relapse (P = 0.004); elevations of serum C-reactive protein (CRP) (P = 0.003) and lactate dehydrogenase (P = 0.029), anaemia (P = 0.029) and they more often completed two transplants within 12 months (P = 0.019). Postenrolment overall survival (OS) and event-free survival (EFS) were superior in the absence of CA of the hypodiploidy or deletion 13 variety (P < 0.001 and 0.037 respectively) and in the presence of low CRP at baseline (P = 0.001 and 0.017 respectively). Postrelapse survival was longer in the absence of CA at relapse (P < 0.001), IgA isotype (P = 0.002), International Staging System stage 3 (P = 0.014), and when patients had two protocol transplants prior to relapse (P = 0.038). Ten-year EFS and OS could be accomplished in 15% and 33% of patients, respectively, when all agents available in 1989, especially high-dose melphalan, were applied together upfront for the management of myeloma.British Journal of Haematology 11/2006; 135(2):158-64. · 4.94 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: 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.Haematologica 05/2010; 95(10):1738-44. · 5.94 Impact Factor