2018
Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma
Tun HW, Johnston PB, DeAngelis LM, Atherton PJ, Pederson LD, Koenig PA, Reeder CB, Omuro AMP, Schiff D, O'Neill B, Pulido J, Jaeckle KA, Grommes C, Witzig TE. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood 2018, 132: 2240-2248. PMID: 30262659, PMCID: PMC6265643, DOI: 10.1182/blood-2018-02-835496.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaOverall response ratePrimary vitreoretinal lymphomaProgression-free survivalRefractory primary central nervous system lymphomaComplete responsePartial responseVitreoretinal lymphomaGrade 3/4 hematologic toxicitiesGrade 3/4 nonhematologic toxicitiesMedian progression-free survivalCentral nervous system lymphomaDose escalation schedulePhase 1 studyNervous system lymphomaCombination of pomalidomideSignificant therapeutic activityMTD cohortNonhematologic toxicityHematologic toxicityRespiratory failureSystem lymphomaMTD determinationPrimary CNSSafety profileMulticenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas.
Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, Terziev R, Kaley TJ, DeAngelis LM, Daras M, Gavrilovic IT, Mellinghoff I, Diamond EL, McKeown A, Manne M, Caterfino A, Patel K, Bavisotto L, Gorman G, Lamson M, Gutin P, Tabar V, Chakravarty D, Chan TA, Brennan CW, Garrett-Mayer E, Karmali RA, Pentsova E. Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. Journal Of Clinical Oncology 2018, 36: 1702-1709. PMID: 29683790, PMCID: PMC5993168, DOI: 10.1200/jco.2017.76.9992.Peer-Reviewed Original ResearchConceptsAnaplastic gliomasCohort 2Cohort 1Median progression-free survivalFavorable brain penetrationMedian overall survivalPhase Ib studyPhase Ib trialPhase II doseProgression-free survivalRecurrent anaplastic gliomasDependent calcium channelsNovel oral inhibitorSignal of activityMismatch repair genesIb trialTreat populationMethylguanine-DNA methyltransferaseOverall survivalComplete responseFlat doseOral inhibitorBrain penetrationResults FortyTherapeutic concentrations
2017
Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Grommes C, Pastore A, Palaskas N, Tang SS, Campos C, Schartz D, Codega P, Nichol D, Clark O, Hsieh WY, Rohle D, Rosenblum M, Viale A, Tabar VS, Brennan CW, Gavrilovic IT, Kaley TJ, Nolan CP, Omuro A, Pentsova E, Thomas AA, Tsyvkin E, Noy A, Palomba ML, Hamlin P, Sauter CS, Moskowitz CH, Wolfe J, Dogan A, Won M, Glass J, Peak S, Lallana EC, Hatzoglou V, Reiner AS, Gutin PH, Huse JT, Panageas KS, Graeber TG, Schultz N, DeAngelis LM, Mellinghoff IK. Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discovery 2017, 7: 1018-1029. PMID: 28619981, PMCID: PMC5581705, DOI: 10.1158/2159-8290.cd-17-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntineoplastic AgentsCARD Signaling Adaptor ProteinsCentral Nervous System NeoplasmsDrug Resistance, NeoplasmFemaleGuanylate CyclaseHumansLymphoma, B-CellMaleMaximum Tolerated DoseMiddle AgedMutationPiperidinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidinesTreatment OutcomeYoung AdultConceptsPrimary central nervous system lymphomaBruton's tyrosine kinaseB-cell lymphomaRefractory B-cell lymphomaB cell antigen receptorCentral nervous system lymphomaRole of BTKDiffuse large B-cell lymphomaLarge B-cell lymphomaPhase I clinical trialClass BTK inhibitorIncomplete tumor responseNervous system lymphomaToll-like receptorsPI3K/mTORIbrutinib responseCNS lymphomaClinical responseComplete responseReceptor-associated proteinSystem lymphomaActivation markersTumor responseClinical trialsPCNSL cells
2014
AT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL
Lassman A, Grommes C, Panageas K, Iwamoto F, DeAngelis L, Kaley T, Gavrilovic I, Pentsova E, Omuro A, Corpuz C, Briggs S, Otap D, Qin W, Cross J, Mellinghoff I. AT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL. Neuro-Oncology 2014, 16: v16-v16. PMCID: PMC4217814, DOI: 10.1093/neuonc/nou237.35.Peer-Reviewed Original ResearchRecurrent malignant gliomaMalignant gliomasInhibitor therapyHigh-dose erlotinibOngoing complete responseEGFR-TKI erlotinibPopulation of patientsMedian age 58Pilot clinical trialInadequate drug deliveryKinase inhibitor therapyDose erlotinibEligible patientsPulsatile dosingAdverse eventsMedian survivalComplete responseDaily doseTKI erlotinibMedian CmaxAnaplastic gliomasClinical trialsAge 58Surgical armLimited efficacyMethotrexate re-challenge for recurrent primary central nervous system lymphoma
Pentsova E, DeAngelis LM, Omuro A. Methotrexate re-challenge for recurrent primary central nervous system lymphoma. Journal Of Neuro-Oncology 2014, 117: 161-165. PMID: 24481997, PMCID: PMC5256683, DOI: 10.1007/s11060-014-1370-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntimetabolites, AntineoplasticCentral Nervous System NeoplasmsDisease ProgressionDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaleMethotrexateMiddle AgedNeoplasm Recurrence, LocalPrognosisRetreatmentRetrospective StudiesSalvage TherapyTreatment OutcomeConceptsPrimary CNS lymphomaKarnofsky performance scoreProgression-free survivalInitial diagnosisRecurrent primary central nervous system lymphomaPrimary central nervous system lymphomaMedian Karnofsky performance scoreMedian progression-free survivalCentral nervous system lymphomaObjective response rateNervous system lymphomaMedian OSCNS lymphomaFree survivalRecurrent diseaseSalvage treatmentFirst relapsePartial responsePCNSL patientsPrognostic factorsComplete responseMedian ageSystem lymphomaDisease relapseMedian time
2013
Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome
Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A. Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome. Journal Of Clinical Oncology 2013, 31: 3971-3979. PMID: 24101038, PMCID: PMC5569679, DOI: 10.1200/jco.2013.50.4910.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, Murine-DerivedAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsChemoradiotherapyCranial IrradiationCytarabineDisease-Free SurvivalFemaleHumansLymphomaMaleMethotrexateMiddle AgedProcarbazineRituximabTimeTreatment OutcomeVincristineConceptsProgression-free survivalMedian progression-free survivalMedian overall survivalPrimary CNS lymphomaOverall survivalR-MPVComplete responseCNS lymphomaMedian Karnofsky performance scoreMulticenter phase II studyLong-term disease controlEnd pointApparent diffusion coefficientExploratory end pointsKarnofsky performance scorePhase II studyPrimary end pointWhole brain radiotherapyLong-term outcomesWhite matter changesHigh response rateInduction chemotherapyStandard WBRTBrain radiotherapyII study
2012
Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma
Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A, Consortium F. Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leukemia & Lymphoma 2012, 54: 58-61. PMID: 22656234, PMCID: PMC4802006, DOI: 10.3109/10428194.2012.698736.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaRecurrent primary central nervous system lymphomaCentral nervous system lymphomaNervous system lymphomaSystem lymphomaDay 1Prospective multicenter phase II trialMedian progression-free survivalMulticenter phase II studyMulticenter phase II trialAggressive salvage treatmentMedian overall survivalPhase II studyPhase II trialProgression-free survivalCycles of consolidationEvaluable patientsII trialSalvage treatmentII studyImmunocompetent patientsOverall survivalComplete responseRetrospective studyPatients
2010
Primary CNS lymphoma in patients younger than 60: can whole-brain radiotherapy be deferred?
Omuro A, Taillandier L, Chinot O, Sierra del Rio M, Carnin C, Barrie M, Soussain C, Tanguy ML, Choquet S, Leblond V, Hoang-Xuan K, On behalf of the ANOCEF Group (French Neuro-Oncology Association).. Primary CNS lymphoma in patients younger than 60: can whole-brain radiotherapy be deferred? Journal Of Neuro-Oncology 2010, 104: 323-330. PMID: 21170569, DOI: 10.1007/s11060-010-0497-x.Peer-Reviewed Original ResearchConceptsWhole brain radiotherapyHigh-dose chemotherapyProgression-free survivalPrimary central nervous system lymphomaSalvage whole brain radiotherapyComplete responseOverall survivalNeurotoxicity riskMedian progression-free survivalCentral nervous system lymphomaAdditional chemotherapy cyclesEffective salvage treatmentMedian overall survivalStem cell rescuePrimary CNS lymphomaNervous system lymphomaObjective of treatmentChemosensitive diseaseChemosensitive patientsChemotherapy cyclesInduction chemotherapyBrain radiotherapyCNS lymphomaObjective responseSalvage treatment
2007
Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly
Omuro AM, Taillandier L, Chinot O, Carnin C, Barrie M, Hoang-Xuan K. Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly. Journal Of Neuro-Oncology 2007, 85: 207-211. PMID: 17896079, DOI: 10.1007/s11060-007-9397-0.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaIntra-thecal chemotherapyFavorable toxicity profileComplete responseToxicity profilePrimary central nervous system lymphomaMedian event-free survivalCentral nervous system lymphomaMedian overall survivalEvent-free survivalNervous system lymphomaNew alternative treatmentLow response rateInduction chemotherapyInnovative regimenCNS lymphomaElderly patientsIntestinal obstructionOverall survivalPCNSL patientsYounger patientsSystem lymphomaConsecutive seriesEfficacy resultsGrade 3
2006
Methotrexate (MTX), procarbazine and CCNU for primary central nervous system lymphoma (PCNSL) in patients younger than 60: Can radiotherapy (RT) be deferred?
Omuro A, Taillandier L, Chinot O, Carnin C, Barrie M, Soussain C, Leblond V, Hoang-Xuan K. Methotrexate (MTX), procarbazine and CCNU for primary central nervous system lymphoma (PCNSL) in patients younger than 60: Can radiotherapy (RT) be deferred? Journal Of Clinical Oncology 2006, 24: 1551-1551. DOI: 10.1200/jco.2006.24.18_suppl.1551.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaHigh-dose chemotherapyProgression-free survivalMedian progression-free survivalOverall survivalComplete responseMaintenance chemotherapySalvage treatmentDay 1Central nervous system lymphomaAcceptable initial approachEffective salvage treatmentGrade 3/4 hematotoxicityMedian overall survivalStem cell rescueFurther treatmentNervous system lymphomaRole of RTIT chemotherapyMedian KPSYounger ptsChemosensitive patientsInduction chemotherapyToxic deathsMedian age
2005
Chemoradiotherapy for primary CNS lymphoma
Omuro AM, DeAngelis LM, Yahalom J, Abrey LE. Chemoradiotherapy for primary CNS lymphoma. Neurology 2005, 64: 69-74. PMID: 15642906, DOI: 10.1212/01.wnl.0000148641.98241.5e.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaLong-term outcomesComplete responsePartial responseCNS lymphomaMedian Karnofsky Performance Scale scoreMedian disease-free survivalProspective phase II trialKarnofsky Performance Scale scoreIncidence of neurotoxicityWhole brain radiotherapyMedian overall survivalDisease-free survivalPhase II trialYear of diagnosisPerformance Scale scoreChemotherapy regimenChemotherapy regimensFifteen patientsFirst relapseII trialMinor complicationsOverall survivalModality treatmentDisease progression