2021
Sustained Improvements in Patient-Reported Quality of Life up to 24 Months Post-Treatment with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Walters M, Tisdale J, Mapara M, Krishnamurti L, Kwiatkowski J, Aygun B, Kasow K, Rifkin-Zenenberg S, Jaroscak J, Garbinsky D, Chirila C, Gallagher M, Zhang X, Ho P, Thompson A, Kanter J. Sustained Improvements in Patient-Reported Quality of Life up to 24 Months Post-Treatment with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy. Blood 2021, 138: 7. DOI: 10.1182/blood-2021-146905.Peer-Reviewed Original ResearchPain intensity numeric rating scaleNumeric rating scaleVaso-occlusive eventsSickle cell diseasePatient-reported outcomesCurrent equity holderMonth 24Severe vaso-occlusive eventsBaseline scoresQuality of lifeBluebird BioPopulation normsException of anxietyComplete resolutionGroup CSmall sample size limits interpretationMean pain interference scoreSevere sickle cell diseaseUS general population normsAdvisory CommitteePatient-reported QOL outcomesMean pain interferencePain interference scoresPain intensity scoresGroup C patientsPolyclonality Strongly Correlates with Biological Outcomes and Is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy (GT)
Tisdale J, Thompson A, Mapara M, Kwiatkowski J, Krishnamurti L, Aygun B, Kasow K, Rifkin-Zenenberg S, Schmidt M, Pierciey F, Whitney D, Rogers C, Nnamani M, Foos M, Miller A, Zhang X, Lynch J, Walters M, Kanter J, Bonner M. Polyclonality Strongly Correlates with Biological Outcomes and Is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy (GT). Blood 2021, 138: 561. DOI: 10.1182/blood-2021-147760.Peer-Reviewed Original ResearchAcute myeloid leukemiaVaso-occlusive eventsCurrent equity holderSevere vaso-occlusive eventsGroup AGroup CMonth 6Clinical outcomesBluebird BioClinical benefitBusulfan conditioningCell doseRisk of AMLAutologous stem cell transplantTricuspid regurgitant jet velocityAdvisory CommitteeDriver mutationsLentiviral vectorsAML driver mutationsOpioid withdrawal syndromeSerious adverse eventsRegurgitant jet velocityFavorable clinical outcomeConsultancy feesStem cell transplant
2020
Improvements in Health-Related Quality of Life for Patients Treated with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Kanter J, Tisdale J, Mapara M, Kwiatkowski J, Krishnamurti L, Chen R, Gallagher M, Ding Y, Goyal S, Paramore C, Thompson A, Walters M. Improvements in Health-Related Quality of Life for Patients Treated with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy. Blood 2020, 136: 10. DOI: 10.1182/blood-2020-136193.Peer-Reviewed Original ResearchSickle cell diseaseAcute chest syndromeNumeric rating scalePatient-reported outcomesMonth 12Pain intensitySleep disturbance domainsBaseline scoresPhysical functionBluebird BioPopulation normsMeaningful improvementsMonth 6Pain intensity numeric rating scalePROMIS-57T-scorePatient-reported HRQoL outcomesUS general population normsAdvisory CommitteePain interference scoresGene therapyGroup C patientsCohort of patientsHealth-related qualityHistory of strokeResolution of Serious Vaso-Occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Thompson A, Walters M, Mapara M, Kwiatkowski J, Krishnamurti L, Aygun B, Kasow K, Rifkin-Zenenberg S, Schmidt M, DelCarpini J, Pierciey F, Miller A, Gallagher M, Chen R, Goyal S, Kanter J, Tisdale J. Resolution of Serious Vaso-Occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy. Blood 2020, 136: 16-17. DOI: 10.1182/blood-2020-134940.Peer-Reviewed Original ResearchAcute chest syndromeVaso-occlusive crisisSickle cell diseaseVaso-occlusive eventsPain intensity scoresGroup C patientsAdverse eventsPain intensityBluebird BioC patientsLast visitBusulfan conditioningHemolysis markersTotal HbIntensity scoresAcute vaso-occlusive painBackground Sickle cell diseasePathophysiology of SCDVaso-occlusive pain crisesPopulation normsPatient-reported pain intensityAdvisory CommitteeGene therapy×109/LAbnormal sickle hemoglobin
2019
Resolution of Sickle Cell Disease Manifestations in Patients Treated with Lentiglobin Gene Therapy: Updated Results from the Phase 1/2 Hgb-206 Group C Study
Kanter J, Tisdale J, Mapara M, Kwiatkowski J, Krishnamurti L, Schmidt M, Miller A, Pierciey F, Huang W, Ribeil J, Thompson A, Walters M. Resolution of Sickle Cell Disease Manifestations in Patients Treated with Lentiglobin Gene Therapy: Updated Results from the Phase 1/2 Hgb-206 Group C Study. Blood 2019, 134: 990. DOI: 10.1182/blood-2019-128894.Peer-Reviewed Original ResearchGroup C patientsRed blood cell transfusionBlood cell transfusionAdverse eventsC patientsMedian Hb levelHb levelsBluebird BioHematopoietic stem cellsCell transfusionLast visitBusulfan conditioningTotal hemoglobinHSC collectionGene therapyNon-hematologic gradeSerious adverse eventsLentiviral vectorsSickle cell diseaseStrong therapeutic effectVector copy numberCancer Research CenterAdditional patient dataAdvisory CommitteeSevere SCD
2018
Outcomes for Initial Patient Cohorts with up to 33 Months of Follow-up in the Hgb-206 Phase 1 Trial
Kanter J, Tisdale J, Kwiatkowski J, Krishnamurti L, Mapara M, Schmidt M, Miller A, Pierciey F, Shi W, Ribeil J, Walters M, Thompson A. Outcomes for Initial Patient Cohorts with up to 33 Months of Follow-up in the Hgb-206 Phase 1 Trial. Blood 2018, 132: 1080. DOI: 10.1182/blood-2018-99-113477.Peer-Reviewed Original ResearchSevere sickle cell diseaseGroup B patientsSickle cell diseaseGroup A patientsB patientsAdverse eventsGroup ALast visitTotal bilirubinBluebird BioHematopoietic stem cellsA patientsPeripheral bloodBusulfan conditioningReticulocyte countTotal HbVeno-occlusive liver diseaseAdvisory CommitteeMedical directorsNormalization of HbVaso-occlusive painSerious adverse eventsLong-term followPhase 1 trialSignificant clinical benefitCurrent Results of Lentiglobin Gene Therapy in Patients with Severe Sickle Cell Disease Treated Under a Refined Protocol in the Phase 1 Hgb-206 Study
Tisdale J, Kanter J, Mapara M, Kwiatkowski J, Krishnamurti L, Schmidt M, Miller A, Pierciey F, Shi W, Ribeil J, Asmal M, Thompson A, Walters M. Current Results of Lentiglobin Gene Therapy in Patients with Severe Sickle Cell Disease Treated Under a Refined Protocol in the Phase 1 Hgb-206 Study. Blood 2018, 132: 1026. DOI: 10.1182/blood-2018-99-113480.Peer-Reviewed Original ResearchSevere sickle cell diseaseSickle cell diseaseNon-cardiac chest painVaso-occlusive painAdverse eventsHb levelsBluebird BioHematopoietic stem cellsHSC collectionDP infusionChest painMyeloablative conditioningPlatelet engraftmentCell diseaseGroup CAdvisory CommitteeMedical directorsGene therapyMonths of transfusionNon-hematologic gradeGroup C patientsSerious adverse eventsSubstantial clinical benefitLentiviral vectorsAdministration of Rimiducid Following Haploidentical BPX-501 Cells in Children with Malignant or Non-Malignant Disorders Who Develop Graft-Versus-Host-Disease (GvHD)
Elkeky R, Jacobsohn D, Agarwal R, Naik S, Kapoor N, Krishnamurti L, Slatter M, Galaverna F, Merli P, Aldinger M, Locatelli F. Administration of Rimiducid Following Haploidentical BPX-501 Cells in Children with Malignant or Non-Malignant Disorders Who Develop Graft-Versus-Host-Disease (GvHD). Blood 2018, 132: 2207. DOI: 10.1182/blood-2018-99-119792.Peer-Reviewed Original ResearchNon-malignant disordersHematopoietic stem cell transplantationTreatment of GVHDDonor T cellsΑβ T cellsT cellsHaplo-HSCTImmune recoveryAdoptive transferPediatric patientsMedian timeB cellsAllogeneic hematopoietic stem cell transplantationOverall clinical response rateConventional steroid therapyEfficacy-evaluable populationOnset of GVHDSteroid-refractory GVHDClinical response rateHLA-compatible donorsStem cell transplantStem cell transplantationΑβ T cell receptorAdvisory CommitteeEffective treatment approach
2017
Successful Plerixafor-Mediated Mobilization, Apheresis, and Lentiviral Vector Transduction of Hematopoietic Stem Cells in Patients with Severe Sickle Cell Disease
Tisdale J, Pierciey F, Kamble R, Kanter J, Krishnamurti L, Kwiatkowski J, Thompson A, Shestopalov I, Bonner M, Joseney-Antoine M, Asmal M, Walters M. Successful Plerixafor-Mediated Mobilization, Apheresis, and Lentiviral Vector Transduction of Hematopoietic Stem Cells in Patients with Severe Sickle Cell Disease. Blood 2017, 130: 990. DOI: 10.1182/blood.v130.suppl_1.990.990.Peer-Reviewed Original ResearchSevere sickle cell diseaseSevere SCDPhase 1 studyBM harvestAutologous hematopoietic stem cellsSickle cell diseaseBone marrowBluebird BioHematopoietic stem cellsCell diseaseCultured CD34Cells/G-CSFPeak white blood cellAdvisory CommitteeMedical directorsHSC mobilizationGene therapyGrade 3 AEsPeripheral blood apheresisGroup B patientsAcceptable toxicity profileLife-threatening complicationsTotal blood volumeSteady-state bone marrow
2016
Interim Results from a Phase 1/2 Clinical Study of Lentiglobin Gene Therapy for Severe Sickle Cell Disease
Kanter J, Walters M, Hsieh M, Krishnamurti L, Kwiatkowski J, Kamble R, von Kalle C, Kuypers F, Cavazzana M, Leboulch P, Joseney-Antoine M, Asmal M, Thompson A, Tisdale J. Interim Results from a Phase 1/2 Clinical Study of Lentiglobin Gene Therapy for Severe Sickle Cell Disease. Blood 2016, 128: 1176. DOI: 10.1182/blood.v128.22.1176.1176.Peer-Reviewed Original ResearchSevere sickle cell diseaseSevere SCDBone marrow harvestAdverse eventsSickle cell diseaseCell doseBluebird BioReplication-competent lentivirusHematopoietic stem cellsMyeloablative conditioningPeripheral bloodCell diseaseGrade 3 adverse eventsAdvisory CommitteeMedical directorsPhase 1/2 clinical studyTransfusion-dependent β-thalassemiaSerious adverse eventsLong-term complicationsVector copy numberStart of conditioningSymptoms 1 yearIntegration site analysisGene therapyDP infusion
2015
Initial Results from Study Hgb-206: A Phase 1 Study Evaluating Gene Therapy By Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the Lentiglobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease
Kanter J, Walters M, Hsieh M, Thompson A, Krishnamurti L, Kwiatkowski J, Kamble R, von Kalle C, Kuypers F, Cavazzana M, Leboulch P, Sandler L, Soni S, Tisdale J. Initial Results from Study Hgb-206: A Phase 1 Study Evaluating Gene Therapy By Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the Lentiglobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease. Blood 2015, 126: 3233. DOI: 10.1182/blood.v126.23.3233.3233.Peer-Reviewed Original ResearchSevere SCDSevere sickle cell diseaseSickle cell diseaseCell diseaseBluebird BioAdverse eventsAutologous CD34Additional subjectsLentiviral vectorsBone marrow harvestVector copy numberIntegration site analysisAdvisory CommitteeGene therapyHematologic engraftmentPRBC transfusionIntravenous busulfanChronic transfusionHb levelsSafety profileAutologous transplantationCell doseStudy visitMonth postProduct infusion
2014
PETIT and PETIT 2: Treatment with Eltrombopag in 171 Children with Chronic Immune Thrombocytopenia (ITP)
Bussel J, Grainger J, de Miguel P, Despotovic J, Locatelli F, Chotsampancharoen T, Donyush E, Navarro J, Pongtanakul B, Komvilaisak P, Sosothikul D, Blanchette V, Drelichman G, Krishnamurti L, Sirachainan N, Connor P, David M, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Boayue K, Matthews D, Marcello L, Iyengar M, Chan G, Chagin K, Theodore D, Bakshi K, Bailey C. PETIT and PETIT 2: Treatment with Eltrombopag in 171 Children with Chronic Immune Thrombocytopenia (ITP). Blood 2014, 124: 1450. DOI: 10.1182/blood.v124.21.1450.1450.Peer-Reviewed Original ResearchChronic immune thrombocytopeniaImmune thrombocytopeniaThrombopoietin receptor agonistsAdverse eventsPlatelet count responsePlatelet countStudy treatmentITP medicationsSerious AEsPBO groupRandomized periodX ULNReceptor agonistRandomized phaseTreatment groupsMedian average daily doseOral thrombopoietin receptor agonistUpper respiratory tract infectionMost subjectsAdvisory CommitteeDose of eltrombopagEfficacy of eltrombopagPediatric immune thrombocytopeniaPre-existing cataractCommon adverse events
2013
An Analysis Of The Pediatric Sub-Group From The Phase 2 Study Of GMI 1070 – A Novel Agent For The Vaso-Occlusive Crisis Of Sickle Cell Anemia
McCavit T, Krishnamurti L, Hsu L, Quinn C, Odame I, Alvarez O, Driscoll C, Smith-Whitley K, Rhee S, Wun T, Telen M, Thackray H. An Analysis Of The Pediatric Sub-Group From The Phase 2 Study Of GMI 1070 – A Novel Agent For The Vaso-Occlusive Crisis Of Sickle Cell Anemia. Blood 2013, 122: 2206. DOI: 10.1182/blood.v122.21.2206.2206.Peer-Reviewed Original ResearchVaso-occlusive crisisSerious adverse eventsSickle cell anemiaAcute chest syndromeStudy drugPediatric subjectsAdult subjectsMaintenance dosesOpioid useSecondary outcomesMedian timePlacebo-controlled phase 2 trialCell anemiaRed blood cell transfusionPhase 3 clinical trialsStrong efficacy signalBlood cell transfusionPhase 2 studyPhase 2 trialKaplan-Meier methodVisual analog scaleInitial medical evaluationPan-selectin inhibitorAdvisory CommitteeMinimal safety concerns