2022
Comparative efficacy and tolerability of novel agents vs chemotherapy in relapsed and refractory T-cell lymphomas: a meta-analysis
Shafagati N, Koh M, Boussi L, Park H, Stuver R, Bain P, Foss FM, Shen C, Jain S. Comparative efficacy and tolerability of novel agents vs chemotherapy in relapsed and refractory T-cell lymphomas: a meta-analysis. Blood Advances 2022, 6: 4740-4762. PMID: 35816645, PMCID: PMC9631658, DOI: 10.1182/bloodadvances.2022007425.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaOverall response rateR Peripheral T Cell LymphomaCombination chemotherapyT-cell lymphomaSingle agentComparative efficacyRefractory T-cell lymphomaPhase ISingle-agent strategyPhase II trialPlatinum-based regimensPhase III trialsPhase I trialOptimal treatment strategyNovel single agentsRandom-effects modelSignificant subgroup differencesII trialIII trialsI trialHistological subtypesTreatment paradigmClinical trialsDrug classes
2021
A Global Phase 2 Study of Valemetostat Tosylate (Valemetostat) in Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL), Including R/R Adult T-Cell Leukemia/Lymphoma (ATL) - Valentine-PTCL01
Foss F, Porcu P, Horwitz S, Izutsu K, Ishitsuka K, Kato K, Jin J, Du Y, Inoue A. A Global Phase 2 Study of Valemetostat Tosylate (Valemetostat) in Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL), Including R/R Adult T-Cell Leukemia/Lymphoma (ATL) - Valentine-PTCL01. Blood 2021, 138: 2533. DOI: 10.1182/blood-2021-144676.Peer-Reviewed Original ResearchR Peripheral T Cell LymphomaTreatment-emergent adverse eventsPeripheral T-cell lymphomaALK-positive anaplastic large cell lymphomaT-cell lymphomaNon-Hodgkin lymphomaPhase 2 studyOverall response rateKyowa Hakko KirinPersonal feesCohort 1Current equity holderDaiichi SankyoResponse rateSeattle GeneticsOno PharmaceuticalCohort 2Computed tomographyMonomorphic epitheliotropic intestinal T-cell lymphomaActive central nervous system (CNS) involvementADC therapeuticsSerious treatment-emergent adverse eventsRefractory peripheral T-cell lymphomaNodal peripheral T-cell lymphomaAllogeneic hematopoietic cell transplantFinal Results from a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma
Witzig T, Sokol L, Kim W, de la Cruz Vicente F, Caballero D, Advani R, de Oña R, Niebla A, Terol M, Eva D, Bendris N, Ahsan J, Leoni M, Foss F. Final Results from a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma. Blood 2021, 138: 621. DOI: 10.1182/blood-2021-147279.Peer-Reviewed Original ResearchAngioimmunoblastic T-cell lymphomaProgression-free survivalOverall response rateT-cell lymphomaOverall survivalPeripheral T-cell lymphomaT-cell non-Hodgkin lymphomaOpen-label trialPhase 2 studyNegative prognostic factorDuration of responsePotential predictive biomarkersNon-Hodgkin lymphomaT-cell homingProgression of diseasePTCL patientsRefractory PTCLUnacceptable toxicityAdult patientsPrognostic factorsPredictive biomarkersLugano classificationCXCL12 expressionReceptor CXCR4New therapiesNovel Single Agents Are Equivalent to Conventional Chemotherapy Inpatients with Relapsed and Refractory Mature T-Cell Lymphomas: A Meta-Analysis
Shafagati N, Stuver R, Boussi L, Koh M, Park A, Bain P, Foss F, Shen C, Jain S. Novel Single Agents Are Equivalent to Conventional Chemotherapy Inpatients with Relapsed and Refractory Mature T-Cell Lymphomas: A Meta-Analysis. Blood 2021, 138: 1431. DOI: 10.1182/blood-2021-150315.Peer-Reviewed Original ResearchOverall response rateT-cell lymphomaHistological subtypesNovel single agentsSingle agentHistone deacetylase inhibitorsConventional chemotherapyResponse rateCentral RegisterPartial responsePTCL-NOSClinical trialsChemotherapy agentsComparable overall response ratesGeneric inverse variance methodCutaneous T-cell lymphomaPhase IParticular histological subtypeSpeakers bureauCochrane Central RegisterProgression-free survivalMature T-cell lymphomasPI3K/Akt/mTORDuration of responseInverse variance methodEPOCH Is a Safe and Effective Treatment Option for Aggressive T-Cell Lymphomas
Sethi T, Gerstein R, Schiffer M, Amin K, Agarwal S, Foss F. EPOCH Is a Safe and Effective Treatment Option for Aggressive T-Cell Lymphomas. Blood 2021, 138: 4547. DOI: 10.1182/blood-2021-151238.Peer-Reviewed Original ResearchAggressive T-cell lymphomaCutaneous T-cell lymphomaT-cell lymphomaAnaplastic large cell lymphomaSubcutaneous panniculitis-like T-cell lymphomaAngioimmunoblastic T-cell lymphomaAdult T-cell leukemia/lymphomaProgression-free survivalOverall response rateNon-Hodgkin lymphomaResponse rateR settingOverall survivalCR rateAdverse effectsPanniculitis-like T-cell lymphomaGrade 3 adverse effectsGrade 4 adverse effectsMedian progression-free survivalAllogeneic stem cell transplantPeripheral T-cell lymphomaT-cell leukemia/lymphomaYale-New Haven HospitalFirst lineEfficacy of etoposideBelinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma
Johnston PB, Cashen AF, Nikolinakos PG, Beaven AW, Barta SK, Bhat G, Hasal SJ, De Vos S, Oki Y, Deng C, Foss FM. Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma. Experimental Hematology & Oncology 2021, 10: 15. PMID: 33602316, PMCID: PMC7893947, DOI: 10.1186/s40164-021-00203-8.Peer-Reviewed Original ResearchPeripheral T-cell lymphomaOverall response rateT-cell lymphomaAdverse eventsDay 1Untreated peripheral T-cell lymphomaRefractory peripheral T-cell lymphomaMedian relative dose intensityPatient experienced DLTSafety/tolerabilityRelative dose intensityResultsTwenty-three patientsSerious adverse eventsFirst-line treatmentHistone deacetylase inhibitorsExperienced DLTsFebrile neutropeniaStandard CHOPStandard cyclophosphamideDose intensityAdditional patientsMTD doseCHOP combinationPK parametersSame dose
2019
Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study.
Khodadoust MS, Rook AH, Porcu P, Foss F, Moskowitz AJ, Shustov A, Shanbhag S, Sokol L, Fling SP, Ramchurren N, Pierce R, Davis A, Shine R, Li S, Fong S, Kim J, Yang Y, Blumenschein WM, Yearley JH, Das B, Patidar R, Datta V, Cantu E, McCutcheon JN, Karlovich C, Williams PM, Subrahmanyam PB, Maecker HT, Horwitz SM, Sharon E, Kohrt HE, Cheever MA, Kim YH. Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study. Journal Of Clinical Oncology 2019, 38: 20-28. PMID: 31532724, PMCID: PMC6943974, DOI: 10.1200/jco.19.01056.Peer-Reviewed Original ResearchConceptsRefractory mycosis fungoidesSézary syndromeOverall response rateMycosis fungoidesTreatment discontinuationFlare reactionAdvanced MF/SSResponse rateMF/Sézary syndromeMulticenter phase II studyMulticenter phase II trialSeverity-Weighted Assessment ToolHigh PD-1 expressionAdvanced mycosis fungoidesEfficacy of pembrolizumabPrior systemic therapySubsequent clinical responseAdvanced-stage diseasePhase II studyPrimary end pointPD-1 expressionPhase II trialFavorable safety profileTotal mutation burdenLack of responseRandomized Phase III Study of Alisertib or Investigator’s Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma
O’Connor O, Özcan M, Jacobsen ED, Roncero JM, Trotman J, Demeter J, Masszi T, Pereira J, Ramchandren R, Beaven A, Caballero D, Horwitz SM, Lennard A, Turgut M, Hamerschlak N, d’Amore F, Foss F, Kim WS, Leonard JP, Zinzani PL, Chiattone CS, Hsi ED, Trümper L, Liu H, Sheldon-Waniga E, Ullmann CD, Venkatakrishnan K, Leonard EJ, Shustov AR, . Randomized Phase III Study of Alisertib or Investigator’s Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma. Journal Of Clinical Oncology 2019, 37: 613-623. PMID: 30707661, PMCID: PMC6494247, DOI: 10.1200/jco.18.00899.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAurora Kinase AAzepinesDisease ProgressionDisease-Free SurvivalDrug Resistance, NeoplasmEarly Termination of Clinical TrialsFemaleHumansLymphoma, T-Cell, PeripheralMaleMiddle AgedProtein Kinase InhibitorsPyrimidinesRecurrenceTime FactorsYoung AdultConceptsPeripheral T-cell lymphomaRefractory peripheral T-cell lymphomaProgression-free survivalOverall response rateT-cell lymphomaComparator armInvestigational Aurora A kinase inhibitorResponse rateMedian progression-free survivalTwo-year overall survivalRandomized phase III studyRandomized phase III trialIndependent data monitoring committeeEfficacy of alisertibMore prior therapiesSingle-agent comparatorCommon adverse eventsPhase III studyPhase III trialsIndependent central reviewData monitoring committeeDrug discontinuationIntravenous romidepsinOral alisertibPrior therapy
2018
Duvelisib, an oral dual PI3K‐δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study
O'Brien S, Patel M, Kahl BS, Horwitz SM, Foss FM, Porcu P, Jones J, Burger J, Jain N, Allen K, Faia K, Douglas M, Stern HM, Sweeney J, Kelly P, Kelly V, Flinn I. Duvelisib, an oral dual PI3K‐δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study. American Journal Of Hematology 2018, 93: 1318-1326. PMID: 30094870, PMCID: PMC8260004, DOI: 10.1002/ajh.25243.Peer-Reviewed Original ResearchConceptsChronic lymphocytic leukemiaPhase 1 studyTN patientsRR patientsLymphocytic lymphomaLymphocytic leukemiaRefractory chronic lymphocytic leukemiaMedian response durationAdvanced hematologic malignanciesPhase 3 studyOverall response rateCLL/SLLSmall lymphocytic lymphomaPatient's diarrheaExpansion cohortTransaminase elevationHematologic malignanciesPharmacodynamic activityResponse durationPatientsResponse rateΓ inhibitorDuvelisibDual inhibitorLymphomaA Phase I Dose‐Escalation Study of Clofarabine in Patients with Relapsed or Refractory Low‐Grade or Intermediate‐Grade B‐Cell or T‐Cell Lymphoma
Foss FM, Parker T. A Phase I Dose‐Escalation Study of Clofarabine in Patients with Relapsed or Refractory Low‐Grade or Intermediate‐Grade B‐Cell or T‐Cell Lymphoma. The Oncologist 2018, 23: 397-e30. PMID: 29438091, PMCID: PMC5896711, DOI: 10.1634/theoncologist.2017-0658.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaT-cell lymphomaNon-Hodgkin lymphomaOverall response rateIntermediate-grade B-cellB cellsPartial responseResponse ratePhase I dose-escalation studyRefractory acute lymphoblastic leukemiaI dose-escalation studyT-cell non-Hodgkin lymphomaB-cell non-Hodgkin lymphomaPositron emission tomography scanSecond-generation purine nucleoside analogAggressive B-cell lymphomasPhase IDose of clofarabineGrade 3 leukopeniaLow-dose cohortMinimal hematologic toxicityRefractory acute leukemiaRefractory low gradeRefractory lymphoid malignanciesSingle-agent rituximab
2017
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
2015
The use of basiliximab–infliximab combination for the treatment of severe gastrointestinal acute GvHD
Nadeau M, Perreault S, Seropian S, Foss F, Isufi I, Cooper DL. The use of basiliximab–infliximab combination for the treatment of severe gastrointestinal acute GvHD. Bone Marrow Transplantation 2015, 51: 273-276. PMID: 26479982, DOI: 10.1038/bmt.2015.247.Peer-Reviewed Original ResearchConceptsGastrointestinal acute GVHDAcute GVHDGrade IIIAllogeneic stem cell transplantCombination of basiliximabSevere GI GvHDSevere grade IIISteroid-refractory diseaseLong-term survivorsStem cell transplantOverall response rateCurrent retrospective studyChronic GVHDGI GVHDSalvage therapySteroid therapyPrimary diseaseCell transplantMedian timeSignificant morbidityPoor outcomeRetrospective studyGVHDMost deathsNew agentsBelinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study
O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. Journal Of Clinical Oncology 2015, 33: 2492-2499. PMID: 26101246, PMCID: PMC5087312, DOI: 10.1200/jco.2014.59.2782.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsDisease-Free SurvivalDrug Administration ScheduleDrug Resistance, NeoplasmFemaleHistone Deacetylase InhibitorsHumansHydroxamic AcidsInfusions, IntravenousKaplan-Meier EstimateLymphoma, T-Cell, PeripheralMaleMiddle AgedNeoplasm Recurrence, LocalSulfonamidesTreatment OutcomeConceptsPeripheral T-cell lymphomaRefractory peripheral T-cell lymphomaInternational Working Group criteriaOverall response rateT-cell lymphomaPrior therapyOverall survivalGroup criteriaResponse rateEnd pointCommon grade 3Prior systemic therapyPrimary end pointSecondary end pointsNovel histone deacetylase inhibitorStem cell transplantationDuration of responseStandard of careDrug Administration approvalHistone deacetylase inhibitorsEvaluable patientsManageable toxicityAdverse eventsDurable responsesPartial responsePhase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma
Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, Zhang X, Kurman MR, Ballerini R, Liu L, Kim YH. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood 2015, 125: 1883-1889. PMID: 25605368, PMCID: PMC4375715, DOI: 10.1182/blood-2014-09-600924.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaEfficacy of mogamulizumabT-cell lymphomaAnti-CC chemokine receptor 4 monoclonal antibodyFrequent treatment-emergent adverse eventsCutaneous T-cell lymphoma patientsTreatment-emergent adverse eventsT-cell lymphoma patientsSignificant hematologic effectsInfusion-related reactionsPhase 1/2 studyOverall response ratePhase 3 investigationAnti-CCR4 antibodyEvaluable patientsBlood involvementAdverse eventsGrade 1/2Sézary syndromeComplete responseMycosis fungoidesLymphoma patientsHematologic effectsDisease progressionMogamulizumab
2013
A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study
Foss FM, Sjak-Shie N, Goy A, Jacobsen E, Advani R, Smith MR, Komrokji R, Pendergrass K, Bolejack V. A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study. Leukemia & Lymphoma 2013, 54: 1373-1379. PMID: 23278639, DOI: 10.3109/10428194.2012.742521.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaDenileukin diftitoxT-cell lymphomaAdverse eventsOverall survivalFrequent treatment-related adverse eventsUntreated peripheral T-cell lymphomaMedian progression-free survivalMost frequent adverse eventsMulticenter phase II trialTreatment-related adverse eventsTreatment-related deathsFrequent adverse eventsMedian overall survivalPhase II studyPhase II trialProgression-free survivalOverall survival rateOverall response rateITT populationSafety populationII trialII studyMedian durationLarge trials
2012
Pralatrexate: treatment of T-cell non-Hodgkins lymphoma
Parker T, Barbarotta L, Foss F. Pralatrexate: treatment of T-cell non-Hodgkins lymphoma. Future Oncology 2012, 9: 21-29. PMID: 23252560, DOI: 10.2217/fon.12.168.Peer-Reviewed Original ResearchConceptsRefractory peripheral T-cell lymphomaPeripheral T-cell lymphomaT-cell non-Hodgkin lymphomaVitamin B12 supplementationOverall response rateNon-Hodgkin lymphomaT-cell lymphomaPROPEL trialCommon toxicitiesB12 supplementationPatient populationClinical studiesResponse ratePralatrexateUS FDALymphomaMetabolic inhibitorsTreatmentToxicityNauseaThrombocytopeniaDoseTrialsSupplementationWeeksLong‐term follow‐up and survival of cutaneous T‐cell lymphoma patients treated with extracorporeal photopheresis
Knobler R, Duvic M, Querfeld C, Straus D, Horwitz S, Zain J, Foss F, Kuzel T, Campbell K, Geskin L. Long‐term follow‐up and survival of cutaneous T‐cell lymphoma patients treated with extracorporeal photopheresis. Photodermatology Photoimmunology & Photomedicine 2012, 28: 250-257. PMID: 22971190, DOI: 10.1111/j.1600-0781.2012.00689.x.Peer-Reviewed Original ResearchConceptsDuration of responseOverall response rateExtracorporeal photopheresisOverall survivalSkin responseResponse rateImpact of ECPCutaneous T-cell lymphomaMedian overall survivalSurvival of patientsT-cell lymphomaLong-term treatmentECP initiationDurable responsesPivotal trialsPatientsCohortECP treatmentModern criteriaSurvivalTreatmentDiagnosisTrialsMonthsResponse
2006
Biologic Correlates of Response and Survival in Patients with Cutaneous T-Cell Lymphoma Treated with Denileukin Diftitox
Chin KM, Foss FM. Biologic Correlates of Response and Survival in Patients with Cutaneous T-Cell Lymphoma Treated with Denileukin Diftitox. Clinical Lymphoma Myeloma & Leukemia 2006, 7: 199-204. PMID: 17229335, DOI: 10.3816/clm.2006.n.059.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCD4-Positive T-LymphocytesClinical Trials as TopicDiphtheria ToxinFemaleHumansInterleukin-2Interleukin-2 Receptor alpha SubunitLymphoma, T-Cell, CutaneousMaleMiddle AgedMycosis FungoidesReceptors, Interleukin-2Recombinant Fusion ProteinsSkin NeoplasmsTreatment OutcomeConceptsCutaneous T-cell lymphomaAdvanced stage diseaseT-cell lymphomaDenileukin diftitoxMedian survivalBiologic correlatesAdvanced-stage cutaneous T-cell lymphomaResponse ratePhase III registration trialNumber of CD4Single-center seriesAbsolute lymphocyte countOverall response rateT cell populationsCourse of therapyLymphocyte countClinical responseLymphocyte populationsDisease progressionDiftitoxPatientsRegistration trialsHuman interleukinLactate dehydrogenaseSurvival