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dc.contributor.authorCraddock, C
dc.contributor.authorSlade, D
dc.contributor.authorDe Santo, C
dc.contributor.authorWheat, R
dc.contributor.authorFerguson, P
dc.contributor.authorHodgkinson, A
dc.contributor.authorBrock, K
dc.contributor.authorCavenagh, J
dc.contributor.authorIngram, W
dc.contributor.authorDennis, M
dc.contributor.authorMalladi, R
dc.contributor.authorSiddique, S
dc.contributor.authorMussai, F
dc.contributor.authorYap, C
dc.date.accessioned2019-06-05T15:14:29Z
dc.date.issued2019-03
dc.identifier.citationJournal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019, 37 (7), pp. 580 - 588
dc.identifier.issn0732-183X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3256
dc.identifier.eissn1527-7755
dc.identifier.doi10.1200/jco.18.00889
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/m 2 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.
dc.formatPrint-Electronic
dc.format.extent580 - 588
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectRecurrence
dc.subjectAzacitidine
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectTreatment Failure
dc.subjectSalvage Therapy
dc.subjectStem Cell Transplantation
dc.subjectTransplantation, Homologous
dc.subjectProspective Studies
dc.subjectMaximum Tolerated Dose
dc.subjectTime Factors
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectLeukemia, Myeloid, Acute
dc.subjectYoung Adult
dc.subjectUnited Kingdom
dc.subjectLenalidomide
dc.titleCombination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia.
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/jco.18.00889
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of clinical oncology : official journal of the American Society of Clinical Oncology
pubs.issue7
pubs.notesNo embargo
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.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-statusPublished
pubs.volume37
pubs.embargo.termsNo embargo
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorYap, Christinaen


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