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dc.contributor.authorEyre, TA
dc.contributor.authorHildyard, C
dc.contributor.authorHamblin, A
dc.contributor.authorAli, AS
dc.contributor.authorHoulton, A
dc.contributor.authorHopkins, L
dc.contributor.authorRoyston, D
dc.contributor.authorLinton, Kim M
dc.contributor.authorPettitt, A
dc.contributor.authorRule, S
dc.contributor.authorCwynarski, K
dc.contributor.authorBarrington, SF
dc.contributor.authorWarbey, V
dc.contributor.authorWrench, D
dc.contributor.authorBarrans, S
dc.contributor.authorHirst, CS
dc.contributor.authorPanchal, A
dc.contributor.authorRoudier, MP
dc.contributor.authorHarrington, EA
dc.contributor.authorDavies, A
dc.contributor.authorCollins, GP
dc.date.accessioned2019-10-07T15:16:42Z
dc.date.available2019-10-07T15:16:42Z
dc.date.issued2019en
dc.identifier.citationEyre TA, Hildyard C, Hamblin A, Ali AS, Houlton A, Hopkins L, et al. A phase II study to assess the safety and efficacy of the dual mTORC1/2 inhibitor vistusertib in relapsed, refractory DLBCL. Hematol Oncol. 2019 Aug 5.en
dc.identifier.pmid31385336en
dc.identifier.doi10.1002/hon.2662en
dc.identifier.urihttp://hdl.handle.net/10541/622205
dc.description.abstractPatients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1002/hon.2662en
dc.titleA phase II study to assess the safety and efficacy of the dual mTORC1/2 inhibitor vistusertib in relapsed, refractory DLBCLen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentDepartment of Haematology, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxforden
dc.identifier.journalHematological Oncologyen
dc.description.noteen]


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