2024
Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML.
Gyurkocza B, Nath R, Seropian S, Choe H, Litzow M, Abboud C, Koshy N, Stiff P, Tomlinson B, Abhyankar S, Foran J, Hari P, Chen G, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco J, Jamieson K, Silverman M, Van Besien K, Schuster M, Law A, Larkin K, Pandit-Taskar N, Rowley S, Munshi P, Cook R, Levy M, Lazarus H, Sandmaier B, Pagel J, Reddy V, MacDougall J, McNamara K, Spross J, Haeuber E, Vusirikala M, Nahar A, Desai A, Giralt S. Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML. Journal Of Clinical Oncology 2024, jco2302018. PMID: 39298738, DOI: 10.1200/jco.23.02018.Peer-Reviewed Original ResearchEvent-free survivalIntention-to-treat populationIntention-to-treatHazard ratioRR-AMLOverall survivalOlder patientsPhase III open-label trialEvent-free survival HRTreatment-related adverse eventsAllogeneic hematopoietic cell transplantationConventional careIncomplete platelet recoveryOS hazard ratioSecondary end pointsHematopoietic cell transplantationOpen-label trialConventional care groupPretransplant regimenRefractory AMLRelapsed/refractory AMLChemotherapy initiationDismal prognosisPlatelet recoveryCell transplantationLong-Term Follow-Up Demonstrates Ongoing Efficacy Benefit of 131I-Apamistamab-led Allogeneic Hematopoietic Cell Transplantation in Older Patients With Active, R/R AML in the Phase 3 SIERRA Trial
Seropian S, Gyurkocza B, Nath R, Choe H, Litzow M, Abboud C, Koshy N, Stiff P, Tomlinson B, Abhyankar S, Foran J, Abedin S, Chen G, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco J, Jamieson K, Silverman M, Van Besien K, Schuster M, Law A, Mayer S, Lazarus H, Spross J, Li K, Vusirikala M, Sandmaier B, Pagel J, Desai A, Giralt S. Long-Term Follow-Up Demonstrates Ongoing Efficacy Benefit of 131I-Apamistamab-led Allogeneic Hematopoietic Cell Transplantation in Older Patients With Active, R/R AML in the Phase 3 SIERRA Trial. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s173. DOI: 10.1016/s2152-2650(24)00518-4.Peer-Reviewed Original ResearchAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationR/R AMLCell transplantationEfficacy benefitsOlder patientsAML-545 Long-Term Follow-up Demonstrates Ongoing Efficacy Benefit of 131I-Apamistamab-led Allogeneic Hematopoietic Cell Transplantation in Older Patients With Active, R/R AML in the Phase 3 SIERRA Trial
Seropian S, Gyurkocza B, Nath R, Choe H, Litzow M, Abboud C, Koshy N, Stiff P, Tomlinson B, Abhyankar S, Foran J, Abedin S, Chen G, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco J, Jamieson K, Silverman M, Van Besien K, Schuster M, Law A, Mayer S, Lazarus H, Spross J, Li K, Vusirikala M, Sandmaier B, Pagel J, Desai A, Giralt S. AML-545 Long-Term Follow-up Demonstrates Ongoing Efficacy Benefit of 131I-Apamistamab-led Allogeneic Hematopoietic Cell Transplantation in Older Patients With Active, R/R AML in the Phase 3 SIERRA Trial. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s319. DOI: 10.1016/s2152-2650(24)01210-2.Peer-Reviewed Original ResearchAllogeneic hematopoietic cell transplantationR/R AMLHematopoietic cell transplantationFollow-upOverall survivalCell transplantationCC patientsCurative allogeneic hematopoietic cell transplantationOlder patientsControlled phase 3 studiesRefractory acute myeloid leukemiaConventional careMedian overall survivalR/R AML patientsMedian follow-upTotal body irradiationBaseline patient characteristicsAcute myeloid leukemiaAnalysis of efficacyOff-target toxicityLong-term survivorsCD45-expressing cellsData cutoffBody irradiationMucositis rates131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant for Patients with TP53 Mutated R/R AML Results in Significantly Improved Outcomes
Foran J, Gyurkocza B, Nath R, Choe H, Litzow M, Abboud C, Koshy N, Stiff P, Tomlinson B, Abhyankar S, Abedin S, Chen G, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco J, Jamieson K, Magalhaes-Silverman M, van Besien K, Schuster M, Law A, Mayer S, Lazarus H, Spross J, Li K, Nagl N, Brodin P, Vusirikala M, Nahar A, Sandmaier B, Pagel J, Giralt S, Desai A, Seropian S. 131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant for Patients with TP53 Mutated R/R AML Results in Significantly Improved Outcomes. Transplantation And Cellular Therapy 2024, 30: s110-s111. DOI: 10.1016/j.jtct.2023.12.174.Peer-Reviewed Original ResearchHematopoietic cell transplantationAllogeneic hematopoietic cell transplantationTP53 mutationsMedian OSOverall survivalPositive PTCell transplantationCC groupDays post-hematopoietic cell transplantationControlled phase 3 studiesEradication of leukemic cellsPost-hematopoietic cell transplantationImprove outcomesConventional careMedian overall survivalTotal body irradiationPhase 3 studyOutcomes of PTPost hoc analysisR/R AMLBody irradiationAML patientsPrimary endpointCurative therapyRelapse rateDose-Response Demonstrated for Durable Complete Remission Following High-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT in Patients with R/R AML
Chen G, Abboud C, Gyurkocza B, Nath R, Seropian S, Choe H, Litzow M, Koshy N, Stiff P, Tomlinson B, Abhyankar S, Foran J, Abedin S, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco J, Jamieson K, Magalhaes-Silverman M, van Besien K, Schuster M, Law A, Leung E, Chen M, Natwa M, Spross J, Li K, Desai A, Wahl R, Brodin P, Pandit-Taskar N. Dose-Response Demonstrated for Durable Complete Remission Following High-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT in Patients with R/R AML. Transplantation And Cellular Therapy 2024, 30: s114-s115. DOI: 10.1016/j.jtct.2023.12.180.Peer-Reviewed Original ResearchPrimary endpointBone marrowLiver doseDose responseCurative allogeneic hematopoietic cell transplantationDose toleranceControlled phase 3 studiesEradication of leukemic cellsRate of hematologic toxicityAllogeneic hematopoietic cell transplantationConventional careTotal body irradiationPhase 3 studyHematopoietic cell transplantationRadiation dose toleranceDiseased bone marrowDoses to liverRadiation dose responseDose-response relationshipDose to target tissuesRadiation dose to liverAcute GVHDR/R AMLHematologic toxicityComplete remissionTargeted Myeloablative Radiation Using 131I-Apamistamab Prior to Allogeneic Hematopoietic Cell Transplant for Patients with R/R AML Results in Robust Engraftment
Choe H, Nath R, Seropian S, Litzow M, Abboud C, Koshy N, Stiff P, Tomlinson B, Abhyankar S, Foran J, Abedin S, Chen G, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco J, Jamieson K, Silverman M, van Besien K, Schuster M, Law A, Spross J, Li K, Nagl N, Vusirikala M, Nahar A, Desai A, Gyurkocza B. Targeted Myeloablative Radiation Using 131I-Apamistamab Prior to Allogeneic Hematopoietic Cell Transplant for Patients with R/R AML Results in Robust Engraftment. Transplantation And Cellular Therapy 2024, 30: s59-s60. DOI: 10.1016/j.jtct.2023.12.094.Peer-Reviewed Original ResearchHematopoietic cell transplantationAllogeneic hematopoietic cell transplantationTime to neutrophilCC armChronic GVHDDonor chimerismPlatelet engraftmentCell transplantationCumulative incidenceTherapeutic dosesCumulative incidence of grade III-IV acute graft-versus-host diseaseGrade III-IV acute graft-versus-host diseaseIII-IV acute graft-versus-host diseaseIncidence of grade III-IV acute graft-versus-host diseaseCumulative incidence of chronic GVHDCurative allogeneic hematopoietic cell transplantationDays post-hematopoietic cell transplantationAcute graft-versus-host diseaseControlled phase 3 studiesEradication of leukemic cellsGrade III-IV GvHDIncidence of chronic GVHDRadiation dose to marrowGraft-versus-host diseaseMedian time to neutrophil131I-Apamistamab Improves Outcomes in Patients 65 Years and Older with Relapsed or Refractory AML
Nath R, Seropian S, Gyurkocza B, Choe H, Litzow M, Abboud C, Koshy N, Stiff P, Abhyankar S, Foran J, Abedin S, Chen G, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco J, Jamieson K, Silverman M, van Besien K, Schuster M, Law A, Spross J, Li K, Nagl N, Vusirikala M, Nahar A, Desai A, Tomlinson B. 131I-Apamistamab Improves Outcomes in Patients 65 Years and Older with Relapsed or Refractory AML. Transplantation And Cellular Therapy 2024, 30: s54-s55. DOI: 10.1016/j.jtct.2023.12.089.Peer-Reviewed Original ResearchHematopoietic cell transplantationPrimary induction failureAcute myeloid leukemiaHigh-risk featuresNon-relapse mortalityCR/CRp ratesInduction failureCurative allogeneic hematopoietic cell transplantationAcute myeloid leukemia ptsAdverse cytogenetic risk groupControlled phase 3 studiesEradication of leukemic cellsRefractory acute myeloid leukemiaAllogeneic hematopoietic cell transplantationCC armCytogenetic risk groupMultiple high-risk featuresTotal body irradiationPhase 3 studyConventional careHigh-risk populationCompared to 0%BCL2 inhibitorsBody irradiationCell transplantation
2022
Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease
Bleakley M, Sehgal A, Seropian S, Biernacki MA, Krakow EF, Dahlberg A, Persinger H, Hilzinger B, Martin PJ, Carpenter PA, Flowers ME, Voutsinas J, Gooley TA, Loeb K, Wood BL, Heimfeld S, Riddell SR, Shlomchik WD. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease. Journal Of Clinical Oncology 2022, 40: 1174-1185. PMID: 35007144, PMCID: PMC8987226, DOI: 10.1200/jco.21.01755.Peer-Reviewed Original ResearchConceptsChronic GVHDAcute GVHDHost diseaseNonrelapse mortalityT cellsPeripheral blood stem cell graftsBlood stem cell graftsGrade II acute GVHDGrade III acute GVHDNaive T-cell depletionAllogeneic hematopoietic cell transplantationPhase II clinical trialChronic Graft-VersusUnrelated donor graftsT-cell depletionHematopoietic cell transplantationTotal body irradiationMemory T cellsRelapse-free survivalStem cell graftsNaive T cellsApparent excess riskCell transplantation approachesGastrointestinal GVHDGraft-Versus
2020
High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Gyurkocza B, Nath R, Choe H, Seropian S, Stiff P, Abhyankar S, Agura E, Litzow M, Tomlinson B, Chen G, Hari P, Orozco J, Al-Kadhimi Z, Abboud C, Van Besien K, Sabloff M, Magalhaes-Silverman M, Foran J, Schuster M, Kebriaei P, Levy M, Lazarus H, Giralt S, Liang Q, Berger M, Reddy V, Pagel J. High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia. Blood 2020, 136: 30-31. DOI: 10.1182/blood-2020-134624.Peer-Reviewed Original ResearchHematopoietic cell transplantationAcute myeloid leukemiaCurrent equity holderR AMLFebrile neutropeniaTherapeutic doseGI tractBone marrowConventional careOlder patientsMyeloid leukemiaRefractory (R/R) AMLHigh-risk acute myeloid leukemiaLow-dose total body irradiationHigh dosesRadiation doseMyeloablative hematopoietic cell transplantationRefractory acute myeloid leukemiaAllogeneic hematopoietic cell transplantationAdvisory CommitteeAEs of interestIncidence of mucositisRate of mucositisInitiation of therapyMedian radiation dosePersonalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered
Gyurkocza B, Nath R, Choe H, Seropian S, Stiff P, Abhyankar S, Agura E, Litzow M, Tomlinson B, Chen G, Hari P, Orozco J, Al-Kadhimi Z, Abboud C, Van Besien K, Sabloff M, Magalhaes-Silverman M, Foran J, Schuster M, Kebriaei P, Levy M, Lazarus H, Giralt S, Liang Q, Berger M, Reddy V, Pagel J. Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered. Blood 2020, 136: 42-44. DOI: 10.1182/blood-2020-134948.Peer-Reviewed Original ResearchAllogeneic hematopoietic cell transplantationR AMLHematopoietic cell transplantationAcute myeloid leukemiaCurrent equity holderComplete remissionTherapeutic doseMarrow blastsOlder patientsCC patientsDelivery of radiationSalvage therapyPlatelet engraftmentRadiation doseRefractory (R/R) AMLHigh-risk acute myeloid leukemiaLow-dose total body irradiationDonor hematopoietic cell engraftmentAdvisory CommitteeSeattle GeneticsAdequate organ functionFull donor chimerismReduced intensity conditioningPhase 3 trialBone marrow blastsTargeted Conditioning with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Leads to High Rates of Allogeneic Transplantation and Successful Engraftment in Older Patients with Active, Relapsed or Refractory (rel/ref) AML after Failure of Chemotherapy and Targeted Agents: Preliminary Midpoint Results from the Prospective, Randomized Phase 3 Sierra Trial
Gyurkocza B, Nath R, Stiff P, Agura E, Litzow M, Tomlinson B, Choe H, Abhyankar S, Seropian S, Chen G, Hari P, Al-Kadhimi Z, Foran J, Orozco J, van Besien K, Sabloff M, Kebriaei P, Abboud C, Levy M, Lazarus H, Giralt S, Berger M, Reddy V, Pagel J. Targeted Conditioning with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Leads to High Rates of Allogeneic Transplantation and Successful Engraftment in Older Patients with Active, Relapsed or Refractory (rel/ref) AML after Failure of Chemotherapy and Targeted Agents: Preliminary Midpoint Results from the Prospective, Randomized Phase 3 Sierra Trial. Transplantation And Cellular Therapy 2020, 26: s32-s33. DOI: 10.1016/j.bbmt.2019.12.575.Peer-Reviewed Original ResearchHematopoietic cell transplantationSalvage therapyOlder patientsCC armConventional careCC patientsConventional hematopoietic cell transplantationGrade 3 febrile neutropeniaAllogeneic hematopoietic cell transplantationPre-treated patientsPhase 3 trialFailure of chemotherapyYears of ageFebrile neutropeniaInduction therapyActive diseaseMyeloablative conditioningRefractory AMLBackground PatientsBM blastsInfusion reactionsMethods PatientsTransplant candidatesAllogeneic transplantationCurative therapy
2019
Re-Induction and Targeted Conditioning with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Leads to High Rates of Transplantation and Successful Engraftment in Older Patients with Active, Relapsed or Refractory (rel/ref) AML after Failure of Chemotherapy and Targeted Agents: Preliminary Midpoint Results from the Prospective, Randomized Phase 3 Sierra Trial
Gyurkocza B, Nath R, Stiff P, Agura E, Litzow M, Tomlinson B, Choe H, Abhyankar S, Seropian S, Chen G, Hari P, Al-Kadhimi Z, Foran J, Orozco J, Van Besien K, Sabloff M, Kebriaei P, Levy M, Lazarus H, Giralt S, Berger M, Reddy V, Pagel J. Re-Induction and Targeted Conditioning with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Leads to High Rates of Transplantation and Successful Engraftment in Older Patients with Active, Relapsed or Refractory (rel/ref) AML after Failure of Chemotherapy and Targeted Agents: Preliminary Midpoint Results from the Prospective, Randomized Phase 3 Sierra Trial. Blood 2019, 134: 5642. DOI: 10.1182/blood-2019-122776.Peer-Reviewed Original ResearchHematopoietic cell transplantationComplete remissionSalvage therapyCC armJazz PharmaceuticalsSpeakers bureauEligible patientsFebrile neutropeniaBM blastsConventional careCC patientsPatient populationGrade 3 febrile neutropeniaGrade 3 infusion reactionsPre-treated patient populationAllogeneic hematopoietic cell transplantationAdvisory CommitteeSeattle GeneticsAdequate organ functionDurable complete remissionPre-treated patientsPhase 3 trialProportion of patientsReduced intensity conditioningLack of efficacy
2018
Targeted Conditioning of Iomab-B (131I-anti-CD45) Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Relapsed or Refractory Acute Myeloid Leukemia (AML): Preliminary Feasibility and Safety Results from the Prospective, Randomized Phase 3 Sierra Trial
Agura E, Gyurkocza B, Nath R, Litzow M, Tomlinson B, Abhyankar S, Seropian S, Stiff P, Choe H, Kebriaei P, Foran J, Chen G, Levy M, Lazarus H, Giralt S, Berger M, Reddy V, Pagel J. Targeted Conditioning of Iomab-B (131I-anti-CD45) Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Relapsed or Refractory Acute Myeloid Leukemia (AML): Preliminary Feasibility and Safety Results from the Prospective, Randomized Phase 3 Sierra Trial. Blood 2018, 132: 1017. DOI: 10.1182/blood-2018-99-111914.Peer-Reviewed Original ResearchHematopoietic cell transplantationAcute myeloid leukemiaR AMLRefractory acute myeloid leukemiaDurable complete remissionComplete remissionActive diseaseYears of ageSalvage therapyDonor chimerismCC armGrade 3Myeloid leukemiaDay 28Frequent non-hematologic adverse eventsNon-hematologic adverse eventsAllogeneic hematopoietic cell transplantationAdequate organ functionR AML patientsStandard induction therapyInfusion-related reactionsPrimary efficacy endpointBone marrow blastsTotal body irradiationOngoing multicenter trial
2000
Chronic graft‐versus‐host disease of the liver: Presentation as an acute hepatitis
Strasser S, Shulman H, Flowers M, Reddy R, Margolis D, Prumbaum M, Seropian S, McDonald G. Chronic graft‐versus‐host disease of the liver: Presentation as an acute hepatitis. Hepatology 2000, 32: 1265-1271. PMID: 11093733, DOI: 10.1053/jhep.2000.20067.Peer-Reviewed Original ResearchConceptsSmall bile ductsBile ductChronic graftHost diseaseAcute hepatitisLiver dysfunctionAlanine transaminaseHigh-dose immunosuppressive therapyProgressive bile duct destructionAllogeneic hematopoietic cell transplantationBile duct destructionChronic liver GVHDHigh-dose immunosuppressionAcute viral hepatitisHematopoietic cell transplantationSerum alanine transaminaseCholestatic pictureChronic GVHDEye involvementImmunosuppressive medicationsLiver GVHDLobular hepatitisMedian bilirubinNecroinflammatory fociDuct destruction