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dc.contributor.authorCraddock, Cen_US
dc.contributor.authorSlade, Den_US
dc.contributor.authorDe Santo, Cen_US
dc.contributor.authorWheat, Ren_US
dc.contributor.authorFerguson, Pen_US
dc.contributor.authorHodgkinson, Aen_US
dc.contributor.authorBrock, Ken_US
dc.contributor.authorCavenagh, Jen_US
dc.contributor.authorIngram, Wen_US
dc.contributor.authorDennis, Men_US
dc.contributor.authorMalladi, Ren_US
dc.contributor.authorSiddique, Sen_US
dc.contributor.authorMussai, Fen_US
dc.contributor.authorYap, Cen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-06-05T15:14:29Z
dc.date.issued2019-03-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30653424en_US
dc.identifier.citationJ Clin Oncol, 2019, 37 (7), pp. 580 - 588en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3256
dc.identifier.eissn1527-7755en_US
dc.identifier.doi10.1200/JCO.18.00889en_US
dc.description.abstractPURPOSE: Salvage options for patients who relapse after allogeneic stem-cell transplantation (allo-SCT) for acute myeloid leukemia (AML) and myelodysplasia (MDS) remain limited, and novel treatment strategies are required. Both lenalidomide (LEN) and azacitidine (AZA) possess significant antitumor activity effect in AML. Administration of LEN post-transplantation is associated with excessive rates of graft-versus-host disease (GVHD), but AZA has been shown to ameliorate GVHD in murine transplantation models. We therefore examined the tolerability and activity of combined LEN/AZA administration in post-transplantation relapse. PATIENTS AND METHODS: Twenty-nine patients who had relapsed after allo-SCT for AML (n = 24) or MDS (n = 5) were treated with sequential AZA (75 mg/m2 for 7 days) followed by escalating doses of LEN on days 10 to 30. Dose allocation and maximum tolerated dose (MTD) estimation were guided by a modified Bayesian continuous reassessment method (CRM). RESULTS: Sequential AZA and LEN therapy was well tolerated. The MTD of post-transplantation LEN, in combination with AZA, was determined as 25 mg daily. Three patients developed grade 2 to 4 GVHD. There was no GVHD-related mortality. Seven of 15 (47%) patients achieved a major clinical response after LEN/AZA therapy. CD8+ T cells demonstrated impaired interferon-γ/tumor necrosis factor-α production at relapse, which was not reversed during LEN/AZA administration. CONCLUSION: We conclude LEN can be administered safely post-allograft in conjunction with AZA, and this combination demonstrates clinical activity in relapsed AML/MDS without reversing biologic features of T-cell exhaustion. The use of a CRM model delivered improved efficiency in MTD assessment and provided additional flexibility. Combined LEN/AZA therapy represents a novel and active salvage therapy in patients who had relapsed post-allograft.en_US
dc.format.extent580 - 588en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleCombination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/JCO.18.00889en_US
rioxxterms.licenseref.startdate2019-03-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJ Clin Oncolen_US
pubs.issue7en_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.publication-statusPublisheden_US
pubs.volume37en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorYap, Christinaen_US


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