Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma
Horwitz SM, Koch R, Porcu P, Oki Y, Moskowitz A, Perez M, Myskowski P, Officer A, Jaffe JD, Morrow SN, Allen K, Douglas M, Stern H, Sweeney J, Kelly P, Kelly V, Aster JC, Weaver D, Foss FM, Weinstock DM. Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood 2017, 131: 888-898. PMID: 29233821, PMCID: PMC5824337, DOI: 10.1182/blood-2017-08-802470.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overClass I Phosphatidylinositol 3-KinasesClass Ib Phosphatidylinositol 3-KinaseFemaleHumansIsoquinolinesLymphoma, T-Cell, CutaneousLymphoma, T-Cell, PeripheralMaleMaximum Tolerated DoseMiddle AgedPhosphoinositide-3 Kinase InhibitorsPrognosisPurinesSafetySkin NeoplasmsTissue DistributionConceptsT-cell lymphomaPhospho-AktImmunosuppressive M2-like phenotypeCutaneous T-cell lymphomaNonmalignant immune cellsOpen-label studySerum cytokine profilesAcceptable safety profileImmune-mediated effectsPhase 1 trialOverall response rateM1-like phenotypePatient-derived xenograftsTumor-associated macrophagesM2-like phenotypeInflammatory M1-like phenotypeT cell growthRefractory PTCLTransaminase increaseAdverse eventsClinical responseCytokine profileMaculopapular rashComplete responsePreclinical evidenceDuvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies
Flinn IW, O'Brien S, Kahl B, Patel M, Oki Y, Foss FF, Porcu P, Jones J, Burger JA, Jain N, Kelly VM, Allen K, Douglas M, Sweeney J, Kelly P, Horwitz S. Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies. Blood 2017, 131: 877-887. PMID: 29191916, PMCID: PMC6033052, DOI: 10.1182/blood-2017-05-786566.Peer-Reviewed Original ResearchConceptsT-cell lymphomaChronic lymphocytic leukemiaIndolent non-Hodgkin lymphomaOral dual inhibitorAdvanced hematologic malignanciesComplete responseTransaminase increaseHematologic malignanciesRefractory chronic lymphocytic leukemiaPeripheral T-cell lymphomaCutaneous T-cell lymphomaAlanine transaminase increaseHematologic malignancy treatmentDose-escalation phaseSevere adverse eventsPhase 1 studyDual inhibitorOverall response rateLate-stage clinical developmentNon-Hodgkin lymphomaCLL tumor cellsRange of dosesAdverse eventsClinical responseMedian time