Randomized study of continuous high-dose lenalidomide, sequential azacitidine and lenalidomide, or azacitidine in persons 65 years and over with newly-diagnosed acute myeloid leukemia

Abstract

Therapy of acute myeloid leukemia in older persons is associated with poor outcomes because of intolerance to intensive therapy, resistant disease and co-morbidities. This multi-center, randomized, open-label, phase II trial compared safety and efficacy of three therapeutic strategies in patients 65 years or over with newly-diagnosed acute myeloid leukemia: 1) continuous high-dose lenalidomide (n=15); 2) sequential azacitidine and lenalidomide (n=39); and 3) azacitidine only (n=34). The efficacy end point was 1-year survival. Median age was 76 years (range 66–87 years). Thirteen subjects (15%) had prior myelodysplastic syndrome and 41 (47%) had adverse cytogenetics. One-year survival was 21% [95% confidence interval (CI): 0, 43%] with high-dose lenalidomide, 44% (95%CI: 28, 60%) with sequential azacitidine and lenalidomide, and 52% (95%CI: 35, 70%) with azacitidine only. Lenalidomide at a continuous high-dose schedule was poorly-tolerated resulting in a high rate of early therapy discontinuations. Hazard of death in the first four months was greatest in subjects receiving continuous high-dose lenalidomide; hazards of death thereafter were similar. These data do not favor use of continuous high-dose lenalidomide or sequential azacitidine and lenalidomide over the conventional dose and schedule of azacitidine only in patients aged 65 years or over with newly-diagnosed acute myeloid leukemia. (clinicaltrials.gov identifier: 01358734).

Efficacy and safety of lenalidomide for the treatment of acute myeloid leukemia: a systematic review and meta-analysis

“…After exclusion, based on title and abstract, 21 full-text articles were reviewed and eleven observational studies were included. 18 – 20 , 25 – 32 Screening of the reference lists for additional studies or referring articles did not yield any further articles for inclusion. Figure 1 shows a flowchart for study selection.…”

“…Overall, 407 participants took part in the eleven trials included in this meta-analysis. 18 – 20 , 25 – 32 The studies included in this meta-analysis showed high variability in terms of the number of AML patients, ranging from 18 to 66. The median age for AML patients in these studies ranged from 63 to 76 years with the proportion of women ranging from 33% to 57%.…”

“… 19 However, a recent study showed that lenalidomide alone or sequential azacitidine and lenalidomide was no better than azacitidine alone in patients >65 years with newly diagnosed AML. 20 Thus, whether lenalidomide improves treatment response in AML remains controversial. This meta- analysis was designed to evaluate the efficacy and safety of lenalidomide for the treatment of AML.…”

Continuous high dosing of lenalidomide in relapsed, refractory or older newly diagnosed acute myeloid leukemia patients not suitable for other treatment options - results from a phase I study

“…6,7 Recently, the combination treatment of a hypomethylating agent and lenalidomide was reported in AML. 8 In a randomized 3-arm study, lenalidomide was administered at a high dosage as monotherapy (50mg/day for 28 days in the first 2 cycles) or sequentially to azacytidine. Again, poor tolerability and low efficacy was reported in this elderly population with newly diagnosed AML.…”

“…Marie Luise Hütter-Krönke, 1 Walter Fiedler, 2 Andrea Kündgen, 3 Jürgen Krauter, 4,7 Marie von Lilienfeld-Toal, 5,8…”