Sequential azacitidine plus lenalidomide in previously treated elderly patients with acute myeloid leukemia and higher risk myelodysplastic syndrome

Leuk Lymphoma. 2016;57(3):609-15. doi: 10.3109/10428194.2015.1091930. Epub 2015 Oct 13.

Abstract

The outcome of sequential azacitidine with lenalidomide has not been reported in previously treated patients with acute myeloid leukemia (AML) and higher risk myelodysplastic syndrome (MDS). This study describes a phase 2 study evaluating the safety and efficacy of this combination in elderly patients with AML and MDS with prior hypomethylating agent (HMA) and/or immunomodulatory agent exposure. Patients were treated on a 42-day cycle with azacitidine at 75 mg/m2 SQ/IV daily on days 1-7, followed by lenalidomide 50 mg orally daily on days 8-28. The median number of treatment cycles on study was two (range = 1-11). Of 32 evaluable patients, the overall response rate was 25%. Neutropenic fever was the most common serious adverse event, but overall the combination was well-tolerated. The median overall survival (OS) for responders vs non-responders was 9.8 vs 4.0 months, respectively (HR = 0.36, p = 0.016). In conclusion, this combination demonstrated modest clinical activity in this poor risk population.

Keywords: AML; Hypomethylating agent failure; MDS; azacitidine; azanucleosides; lenalidomide.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / administration & dosage
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Biomarkers
  • Bone Marrow / pathology
  • Female
  • Humans
  • Lenalidomide
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / mortality
  • Retreatment
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Biomarkers
  • Thalidomide
  • Lenalidomide
  • Azacitidine