title: Sequential azacitidine plus lenalidomide in previously treated elderly patients with acute myeloid leukemia and higher risk myelodysplastic syndrome.
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.
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Rupa
authors.initials: R
authors.lastname: Narayan
authors.affiliation: b Division of Hematologic Malignancies, Department of Medical Oncology , Dana-Farber Cancer Institute , Boston , MA , USA .
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Garcia
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Mary-Elizabeth M
authors.initials: ME
authors.lastname: Percival
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Caroline
authors.initials: C
authors.lastname: Berube
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Steve
authors.initials: S
authors.lastname: Coutre
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Peter
authors.initials: P
authors.lastname: Greenberg
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Michaela
authors.initials: M
authors.lastname: Liedtke
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Rhonda
authors.initials: R
authors.lastname: Hewitt
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Kathleen
authors.initials: K
authors.lastname: Regan
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Charles
authors.initials: C
authors.lastname: Williamson
authors.affiliation: c Eutropics Pharmaceuticals , Cambridge , MA , USA , and.
authors.forename: Camille
authors.initials: C
authors.lastname: Doykan
authors.affiliation: c Eutropics Pharmaceuticals , Cambridge , MA , USA , and.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cardone
authors.affiliation: d Department of Health Research and Policy , Stanford University School of Medicine , Stanford , CA , USA.
authors.forename: Alex
authors.initials: A
authors.lastname: McMillan
authors.affiliation: a Division of Hematology, Department of Medicine , Stanford University School of Medicine , Stanford , CA , USA .
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D019233:Retreatment; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D015415:Biomarkers; D013792:Thalidomide; D000077269:Lenalidomide; D001374:Azacitidine
keywords: AML; Hypomethylating agent failure; MDS; azacitidine; azanucleosides; lenalidomide