Prior clinical data have suggested that prolonged exposure to lenalidomide is important to improve outcomes both as a maintenance agent posttransplant1,2 and in the transplant-ineligible population.3,4 In the Myeloma XI study, researchers explored the use of oral lenalidomide continued to disease progression compared with no therapy in both newly diagnosed transplant-eligible (TE) and transplant noneligible (TNE) patients.
This phase 3, UK-based, multicenter, open-label, parallel-group, randomized controlled trial included a maintenance comparison of lenalidomide versus no maintenance. Newly diagnosed symptomatic myeloma patients both TE and TNE were enrolled in the study. In both arms, patients received induction treatment with thalidomide or lenalidomide plus cyclophosphamide and dexamethasone, with appropriate dose reductions for TNE patients. TE patients proceeded to a standard melphalan 200-mg/m2 transplant.
Patients were randomized to either maintenance lenalidomide or observation after achieving maximum response (TNE) or at 100 days after transplant (TE). Lenalidomide was administered at a dose of 10 mg daily in 21/28 day cycles until disease progression with dose adjustments for treatment-related toxicity if necessary. The primary end points for the maintenance randomization were progression-free survival (PFS) and overall survival.
A total of 1551 patients, 828 TE and 723 TNE, median age 67 and 66 years, respectively, were randomized between lenalidomide (n = 857) and no maintenance (n = 694). In this analysis, the maintenance randomization met its primary end point, demonstrating a 50% reduction in risk of progression or death for lenalidomide compared with no maintenance (hazard ratio, 0.45; 95% confidence interval, 0.39-0.52; median PFS, 36 versus 18 months; P <0.0001). Significant improvement was observed in both the TE and NTE groups. Furthermore, the benefit of lenalidomide maintenance on PFS persisted across risk subgroups, including patients with high-risk cytogenetics, and was independent of induction therapy and response.
In this ongoing study, 445 patients continue to receive lenalidomide maintenance on study. Grade 3/4 adverse events included neutropenia (33.7%), thrombocytopenia (7.0%), anemia (4.1%), deep vein thrombosis/pulmonary embolism (1.2%), and peripheral neuropathy (1.1%).
Researchers concluded that the use of maintenance lenalidomide treatment results in highly significant improvements in PFS for patients with newly diagnosed MM of all ages.
Jackson GH, et al. ASH 2016. Abstract 1143.
- Attal M, et al. N Engl J Med. 2012.
- McCarthy, et al. N Engl J Med. 2012.
- Palumbo A, et al. N Engl J Med. 2012.
- Benboubker L, et al. N Engl J Med. 2014.