2019
Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D’Angelo S, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics 2019, 51: 202-206. PMID: 30643254, PMCID: PMC6365097, DOI: 10.1038/s41588-018-0312-8.Peer-Reviewed Original ResearchConceptsTumor mutational burdenHigh tumor mutational burdenImproved survivalCancer typesImmune checkpoint inhibitor treatmentAdvanced cancer patientsBetter overall survivalCheckpoint inhibitor treatmentMultiple cancer typesClinical responseOverall survivalCancer patientsPredictive biomarkersCancer histologyMetastatic cancerMutational burdenPatientsInhibitor treatmentNext-generation sequencingSurvivalICIMutational loadUniversal definitionAssociationImmunotherapy
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 cellsUpdated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).
Grommes C, Gavrilovic I, Kaley T, Nolan C, Omuro A, Wolfe J, Pentsova E, Hatzoglou V, Mellinghoff I, DeAngelis L. Updated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL). Journal Of Clinical Oncology 2017, 35: 7515-7515. DOI: 10.1200/jco.2017.35.15_suppl.7515.Peer-Reviewed Original ResearchSecondary CNS lymphomaProgression-free survivalMedian progression-free survivalALT elevationCNS lymphomaAdverse eventsClinical responseGrade 4 adverse eventsRecurrent/refractory diseaseAggressive primary brain tumorCerebrospinal fluid involvementCNS lymphoma patientsGrade 5 eventsManageable adverse eventsGrade 3 toxicityMedian overall survivalMethotrexate-based chemotherapyEnd-organ functionNormal end-organ functionSingle-agent ibrutinibUrinary tract infectionPrimary brain tumorsPromising clinical responsesMantle cell lymphomaCommon toxicities
2016
Single-Agent Ibrutinib in Recurrent/Refractory Central Nervous System Lymphoma
Grommes C, Pastore A, Gavrilovic I, Kaley T, Nolan C, Omuro A, Wolfe J, Pentsova E, Hatzoglou V, Mellinghoff I, DeAngelis L. Single-Agent Ibrutinib in Recurrent/Refractory Central Nervous System Lymphoma. Blood 2016, 128: 783. DOI: 10.1182/blood.v128.22.783.783.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaProgression-free survivalSecondary CNS lymphomaMedian progression-free survivalHigh-dose methotrexate chemotherapyCentral nervous system lymphomaNervous system lymphomaAdverse eventsCNS lymphomaCombination armClinical responseMethotrexate chemotherapySystem lymphomaGrade 4 adverse eventsRecurrent/refractory diseaseAggressive primary brain tumorCerebrospinal fluid involvementCNS lymphoma patientsManageable adverse eventsGrade 3 toxicityMethotrexate-based chemotherapyEnd-organ functionNormal end-organ functionUrinary tract infectionPrimary brain tumorsACTR-12. PHASE I/II STUDY OF SINGLE AGENT IBRUTINIB IN RECURRENT/REFRACTORY PRIMARY (PCNSL) AND SECONDARY CNS LYMPHOMA (SCNSL)
Grommes C, Gavrilovic I, Kaley T, Nolan C, Omuro A, Wolfe J, Pentsova E, Hatzoglou V, Mellinghoff I, DeAngelis L. ACTR-12. PHASE I/II STUDY OF SINGLE AGENT IBRUTINIB IN RECURRENT/REFRACTORY PRIMARY (PCNSL) AND SECONDARY CNS LYMPHOMA (SCNSL). Neuro-Oncology 2016, 18: vi3-vi4. DOI: 10.1093/neuonc/now212.011.Peer-Reviewed Original ResearchSecondary CNS lymphomaCNS lymphomaPhase I/II studyRecurrent/refractory diseaseAggressive primary brain tumorCerebrospinal fluid involvementCNS lymphoma patientsGrade 4 toxicityGrade 3 toxicityEnd-organ functionNormal end-organ functionSingle-agent ibrutinibPrimary brain tumorsPromising clinical responsesB-cell malignanciesCommon toxicitiesEligible patientsFungal encephalitisManageable toxicityMedian PFSMethotrexate regimensPrior therapySCNSL patientsClinical responseII study
2013
Primary leptomeningeal lymphoma
Taylor JW, Flanagan EP, O'Neill BP, Siegal T, Omuro A, DeAngelis L, Baehring J, Nishikawa R, Pinto F, Chamberlain M, Hoang-Xuan K, Gonzalez-Aguilar A, Batchelor T, Blay JY, Korfel A, Betensky RA, Lopes MB, Schiff D. Primary leptomeningeal lymphoma. Neurology 2013, 81: 1690-1696. PMID: 24107866, PMCID: PMC3812109, DOI: 10.1212/01.wnl.0000435302.02895.f3.Peer-Reviewed Original ResearchConceptsPrimary leptomeningeal lymphomaPrimary CNS lymphomaLeptomeningeal lymphomaCNS lymphomaLeptomeningeal enhancementCSF cytologyMedian Eastern Cooperative Oncology Group performance statusRare formEastern Cooperative Oncology Group performance statusInternational Primary CNS Lymphoma Collaborative GroupIntra-CSF chemotherapyMedian overall survivalFavorable clinical responseCases of lymphomaOptimal diagnostic evaluationGene rearrangement studiesB-cell lymphomaMultifocal symptomsSalvage treatmentSystemic chemotherapyClinical responseOverall survivalPerformance statusMedian ageSystemic involvement