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 cellsPhase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
Tun H, Johnston P, Grommes C, Reeder C, Omuro A, Menke D, Copland J, DeAngelis L, Witzig T. Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL). Journal Of Clinical Oncology 2017, 35: 7516-7516. DOI: 10.1200/jco.2017.35.15_suppl.7516.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaOverall response rateRefractory primary central nervous system lymphomaPhase I clinical trialPrimary vitreoretinal lymphomaMTD cohortStable diseaseClinical trialsCentral nervous system lymphomaTherapeutic activityDiffuse large B-cell lymphomaLarge B-cell lymphomaDose level 3Grade 3/4 toxicitiesNovel immunomodulatory agentsNervous system lymphomaCycles of treatmentDose escalation levelsCSF/blood ratioB-cell lymphomaExcellent CNS penetrationPO weeklyPomalidomide treatmentPseudo progressionCNS lymphoma
2014
Autologous stem cell transplant in recurrent or refractory primary or secondary central nervous system lymphoma using thiotepa, busulfan and cyclophosphamide
Welch MR, Sauter CS, Matasar MJ, Faivre G, Weaver SA, Moskowitz CH, Omuro AM. Autologous stem cell transplant in recurrent or refractory primary or secondary central nervous system lymphoma using thiotepa, busulfan and cyclophosphamide. Leukemia & Lymphoma 2014, 56: 361-367. PMID: 24745937, DOI: 10.3109/10428194.2014.916800.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBusulfanCentral Nervous System NeoplasmsCombined Modality TherapyCyclophosphamideDisease-Free SurvivalDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleHumansKaplan-Meier EstimateMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisRemission InductionStem Cell TransplantationThiotepaTransplantation, AutologousTreatment OutcomeConceptsAutologous stem cell transplantProgression-free survivalHigh-dose chemotherapyStem cell transplantOverall survivalCell transplantSecondary central nervous system lymphomaRefractory diffuse large B-cell lymphomaMedian progression-free survivalCentral nervous system involvementCentral nervous system lymphomaDiffuse large B-cell lymphomaLarge B-cell lymphomaTransplant-related mortalityNervous system involvementSecondary CNS lymphomaNervous system lymphomaStem cell harvestingB-cell lymphomaPotential treatment alternativeHDC-ASCTInduction chemotherapyRecurrent primaryCNS lymphomaComplete remission