Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia

Haematologica. 2013 Apr;98(4):591-6. doi: 10.3324/haematol.2012.076414. Epub 2012 Dec 14.

Abstract

There are limited treatment options for older patients with acute myeloid leukemia and prognosis of these patients remains poor, thereby warranting development of novel therapies. We evaluated the efficacy and safety of azacitidine in combination with lenalidomide as front-line therapy for older patients with acute myeloid leukemia. Patients ≥ 60 years of age with untreated acute myeloid leukemia received azacitidine 75 mg/m2 for 7 days followed by escalating doses of lenalidomide daily for 21 days starting on day 8 of each cycle every 6 weeks. Patients received continued therapy until disease progression, unacceptable toxicity, or completion of 12 cycles. Forty-two patients (median age, 74 years) were enrolled with equal distribution according to European LeukemiaNet risk. The overall response rate was 40% (rate of complete remission with or without complete recovery of blood counts = 28%). The median time to complete remission with or without complete recovery of blood counts was 12 weeks, and duration of this status was 28 weeks (range, 4 - >104 weeks). Therapy-related acute myeloid leukemia and a high score on the Hematopoietic Cell Transplantation Comorbidity Index were negative predictors of response. Early death was noted in 17% of patients. Grades ≥ 3 toxicities were uncommon and most adverse events were gastrointestinal, fatigue and myelosuppression. In conclusion, a sequential combination of azacitidine plus lenalidomide has clinical activity in older patients with acute myeloid leukemia, and further studies of this combination are underway.

Trial registration: ClinicalTrials.gov NCT00890929.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lenalidomide
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / pathology
  • Male
  • Middle Aged
  • Mutation
  • Nausea / chemically induced
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Prognosis
  • Remission Induction
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives
  • Treatment Outcome
  • Vomiting / chemically induced
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Nuclear Proteins
  • Nucleophosmin
  • Thalidomide
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Lenalidomide
  • Azacitidine

Associated data

  • ClinicalTrials.gov/NCT00890929