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 transplantationAML-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
40 High Rates of Transplantation in the Phase III Sierra Trial Utilizing Anti-CD45 (Iodine) 131I-Apamistamab (Iomab-B) Conditioning with Successful Engraftment and Tolerability in Relapsed Refractory (R/R) Acute Myeloid Leukemia (AML) Patients after Lack of Response to Conventional Care and Targeted Therapies
Gyurkocza B, Nath R, Seropian S, Choe H, Litzow M, Koshy N, Stiff P, Abboud C, Tomlinson B, Abhyankar S, Hari P, Chen G, Al-Kadhimi Z, Sabloff M, Orozco J, Foran J, Kebriaei P, Jamieson K, Magalhaes-Silverman M, van Besien K, Schuster M, Law A, Levy M, Lazarus H, Giralt S, Berger M, Spross J, Desai A, Reddy V, Pagel J. 40 High Rates of Transplantation in the Phase III Sierra Trial Utilizing Anti-CD45 (Iodine) 131I-Apamistamab (Iomab-B) Conditioning with Successful Engraftment and Tolerability in Relapsed Refractory (R/R) Acute Myeloid Leukemia (AML) Patients after Lack of Response to Conventional Care and Targeted Therapies. Transplantation And Cellular Therapy 2022, 28: s35-s36. DOI: 10.1016/s2666-6367(22)00201-9.Peer-Reviewed Original Research
2021
Clinical Experience in the Randomized Phase 3 Sierra Trial: Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Conditioning Enables Hematopoietic Cell Transplantation with Successful Engraftment and Acceptable Safety in Patients with Active, Relapsed/Refractory AML Not Responding to Targeted Therapies
Gyurkocza B, Nath R, Seropian S, Choe H, Litzow M, Koshy N, Stiff P, Abboud C, Tomlinson B, Abhyankar S, Hari P, Al-Kadhimi Z, Chen G, Sabloff M, Orozco J, Foran J, Kebriaei P, Jamieson K, Magalhaes-Silverman M, van Besien K, Schuster M, Law A, Levy M, Lazarus H, Giralt S, Berger M, Spross J, Desai A, Reddy V, Pagel J. Clinical Experience in the Randomized Phase 3 Sierra Trial: Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Conditioning Enables Hematopoietic Cell Transplantation with Successful Engraftment and Acceptable Safety in Patients with Active, Relapsed/Refractory AML Not Responding to Targeted Therapies. Blood 2021, 138: 1791. DOI: 10.1182/blood-2021-148497.Peer-Reviewed Original ResearchHematopoietic cell transplantAcute myeloid leukemiaR AMLAllogeneic hematopoietic cell transplantComplete remissionMedian radiation doseBristol-Myers SquibbCC patientsTargeted therapyFebrile neutropeniaFLT-3 inhibitorsCurrent equity holderSpeakers bureauConventional careMedian timeBcl-2 inhibitorsIDH inhibitorsRelapsed/Refractory Acute Myeloid LeukemiaIncidence of FNRefractory acute myeloid leukemiaAdvisory CommitteePrincipal investigatorSeattle GeneticsIncidence of gradeIncidence of sepsis
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 doseTargeted 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