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

• Published in: Haematologica (Roma) Vol. 103; no. 1; pp. 101 - 106
• Main Authors: Medeiros, Bruno C., McCaul, Kelly, Kambhampati, Suman, Pollyea, Daniel A., Kumar, Rajat, Silverman, Lewis R., Kew, Andrea, Saini, Lalit, Beach, CL, Vij, Ravi, Wang, Xiwei, Zhong, Jim, Gale, Robert Peter
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.01.2018
• Subjects: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Azacitidine - administration & dosage; Azacitidine - therapeutic use; Female; Humans; Kaplan-Meier Estimate; Lenalidomide - administration & dosage; Lenalidomide - therapeutic use; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - mortality; Male; Proportional Hazards Models; Treatment Outcome
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2017.172353

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. ( ).