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
Preliminary Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia
Smith A, Schiller G, Vercellotti G, Kwiatkowski J, Krishnamurti L, Esrick E, Williams D, Miller W, Woolfson A, Walters M. Preliminary Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia. Blood 2019, 134: 3544. DOI: 10.1182/blood-2019-125743.Peer-Reviewed Original ResearchTransfusion-dependent beta thalassemiaPeripheral blood mononuclear cellsSerious adverse eventsHematopoietic stem cell transplantationHuman hematopoietic stem cellsHematopoietic reconstitutionBluebird BioPRBC transfusionPatient 1HbF levelsG-CSFJazz PharmaceuticalsPacked red blood cell transfusionPhase I/II studyAllogeneic hematopoietic stem cell transplantationRed blood cell transfusionHematopoietic stem cellsPhase 1/2 clinical studyBeta thalassemiaInvestigational cell therapySpeakers bureauBlood cell transfusionStem cell transplantationBlood mononuclear cellsCells/Exploring the Drivers of Potential Clinical Benefit in Initial Patients Treated in the Hgb-206 Study of Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy
Walters M, Tisdale J, Kwiatkowski J, Krishnamurti L, Mapara M, Schmidt M, Miller A, Pierciey F, Huang W, Ribeil J, Kanter J, Thompson A. Exploring the Drivers of Potential Clinical Benefit in Initial Patients Treated in the Hgb-206 Study of Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy. Blood 2019, 134: 2061. DOI: 10.1182/blood-2019-128814.Peer-Reviewed Original ResearchAcute chest syndromeVaso-occlusive crisisGroup A patientsRate of VOCAdverse eventsA patientsPatient 1Group AClinical benefitLast visitBluebird BioHematopoietic stem cellsInitial patientsPatient 2Busulfan conditioningGroup BHbF levelsVeno-occlusive liver diseaseRed blood cell transfusionFull hematological recoveryBlood cell transfusionCases of gradeLentiviral vectorsGene therapyPotential clinical benefitResolution 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 vectors
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