2024
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
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 remission131I-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
2023
131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant Significantly Improves Overall Survival in Patients with TP53 Mutated R/R AML
Choe H, Tomlinson B, Gyurkocza B, Nath R, Seropian S, Litzow M, Abboud C, Stiff P, Abhyankar S, Foran J, 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, Haeuber E, Vusirikala M, Nahar A, Sandmaier B, Pagel J, Giralt S, Desai A, Koshy N. 131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant Significantly Improves Overall Survival in Patients with TP53 Mutated R/R AML. Blood 2023, 142: 469. DOI: 10.1182/blood-2023-182177.Peer-Reviewed Original ResearchMedian overall survivalAllogeneic hematopoietic cell transplantDurable complete remissionHematopoietic cell transplantOverall survivalR AMLConventional careTP53 mutationsPositive ptsCC groupComplete remissionRelapse rateCell transplantHigh post-transplant relapse ratesInitiation of therapyPhase 3 studyTotal body irradiationHigh relapse rateCRP assessmentEvaluable ptsOlder ptsActive diseaseBaseline characteristicsRefractory AMLBody irradiationHigh-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT Demonstrated a Dose-Response for Durable Complete Remission in Patients with R/R AML
Litzow M, Chen G, Gyurkocza B, Nath R, Seropian S, Choe H, Abboud C, Koshy N, 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, Mayer S, Lazarus H, Leung E, Chen M, Natwa M, Spross J, Li K, Nagl N, Haeuber E, Vusirikala M, Nahar A, Sandmaier B, Pagel J, Giralt S, Desai A, Wahl R, Pandit-Taskar N, Brodin P, Stiff P. High-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT Demonstrated a Dose-Response for Durable Complete Remission in Patients with R/R AML. Blood 2023, 142: 3529. DOI: 10.1182/blood-2023-189040.Peer-Reviewed Original ResearchDurable complete remissionConventional careLiver dosePrimary endpointBone marrowR AMLComplete remissionLiver ratioHigh doseLeukemic cellsRadiation doseAllogeneic hematopoietic cell transplantRadiation dose-response relationshipHematopoietic cell transplantMost older patientsPhase 3 studyTotal body irradiationFavorable biodistributionRadiation dose toleranceYears of ageDose toleranceDose-response relationshipDiseased bone marrowMedian doseRefractory AML131I-Apamistamab Effectively Achieved Durable Responses in Patients with R/R AML Irrespective of the Presence of Multiple High-Risk Factors
Seropian S, Foran J, Gyurkocza B, Nath R, Choe H, Litzow M, 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, Haeuber E, Vusirikala M, Nahar A, Sandmaier B, Pagel J, Giralt S, Desai A, Abboud C. 131I-Apamistamab Effectively Achieved Durable Responses in Patients with R/R AML Irrespective of the Presence of Multiple High-Risk Factors. Blood 2023, 142: 2159. DOI: 10.1182/blood-2023-187433.Peer-Reviewed Original ResearchDurable complete remissionAdverse-risk cytogeneticsMultiple risk factorsRisk factorsConventional careCC groupComorbidity indexComplete remissionDurable responsesAllogeneic hematopoietic cell transplantHigh transplant-related mortalityMultiple high-risk factorsPrimary induction failureTransplant-related mortalityHematopoietic cell transplantInitiation of therapyMost older patientsPhase 3 studyHigher comorbidity indexTotal body irradiationHigh-risk factorsMechanism of actionAML ptsCRP assessmentEvaluable pts
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
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
2015
Outcomes of acute leukemia patients transplanted with naive T cell–depleted stem cell grafts
Bleakley M, Heimfeld S, Loeb KR, Jones LA, Chaney C, Seropian S, Gooley TA, Sommermeyer F, Riddell SR, Shlomchik WD. Outcomes of acute leukemia patients transplanted with naive T cell–depleted stem cell grafts. Journal Of Clinical Investigation 2015, 125: 2677-2689. PMID: 26053664, PMCID: PMC4563691, DOI: 10.1172/jci81229.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdolescentAdrenal Cortex HormonesAdultAnimalsChronic DiseaseDisease-Free SurvivalFemaleGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHistocompatibility TestingHumansKaplan-Meier EstimateLeukemiaLymphocyte DepletionMaleMiceMiddle AgedMyelodysplastic SyndromesTissue DonorsT-Lymphocyte SubsetsTransplantation ConditioningTransplantation, HomologousYoung AdultConceptsHematopoietic stem cell transplantationStem cell graftsChronic GVHDT cellsCell graftsT-cell-depleted stem cell graftsPeripheral blood stem cell graftsAllogeneic hematopoietic stem cell transplantationBlood stem cell graftsFunctional T-cell memoryT-cell-replete graftsPathogen-specific T cellsSingle-arm clinical trialT-cell recoveryVirus-specific immunityStem cell allograftsTotal body irradiationMemory T cellsStem cell transplantationT cell memoryAcute leukemia patientsHigh-risk leukemiaNaive T cellsAcute GVHDSevere GVHD