2023
A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents
Bewersdorf J, Shallis R, Sharon E, Park S, Ramaswamy R, Roe C, Irish J, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Annals Of Hematology 2023, 103: 105-116. PMID: 38036712, DOI: 10.1007/s00277-023-05552-4.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAcute myeloid leukemiaMarrow complete remissionPhase Ib trialAdverse eventsIb trialDose escalationNCI Cancer Therapy Evaluation ProgramAcute myeloid leukemia refractoryHematologic adverse eventsProtocol-defined responseDose level 1Anti-PD1 therapyAnti-PD1 antibodyDose-escalation designLimited clinical efficacySystems immunology approachHistone deacetylase inhibitor entinostatLeukemia refractoryMCR patientsComplete remissionRespiratory failureSuppressor cellsEscalation designClinical efficacy
2022
Follow-up of patients with R/R FLT3-mutation–positive AML treated with gilteritinib in the phase 3 ADMIRAL trial
Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Récher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation–positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood 2022, 139: 3366-3375. PMID: 35081255, PMCID: PMC9197557, DOI: 10.1182/blood.2021011583.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSalvage chemotherapyADMIRAL trialSC armOverall survivalFLT3 mutation-positive acute myeloid leukemiaPositive acute myeloid leukemiaComposite complete remissionStable safety profileAdverse event incidenceCommon adverse eventsLiver transaminase levelsMedian overall survivalSuperior overall survivalLong-term treatment effectsGilteritinib armComplete remissionMaintenance therapyAdverse eventsCumulative incidenceMedian survivalTransaminase levelsEvent incidenceMaintenance treatmentSafety profileClinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib
Perl AE, Hosono N, Montesinos P, Podoltsev N, Martinelli G, Panoskaltsis N, Recher C, Smith CC, Levis MJ, Strickland S, Röllig C, Groß-Langenhoff M, Chou WC, Lee JH, Yokoyama H, Hasabou N, Lu Q, Tiu RV, Altman JK. Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Blood Cancer Journal 2022, 12: 84. PMID: 35637252, PMCID: PMC9151663, DOI: 10.1038/s41408-022-00677-7.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaFLT3-TKIRefractory FLT3TKI exposureSalvage chemotherapyClinical outcomesMyeloid leukemiaR AMLLonger median overall survivalComposite complete remissionHigher CRCS ratesMedian overall survivalTyrosine kinase inhibitor midostaurinKinase inhibitor midostaurinPotential clinical impactADMIRAL trialCRC ratesGilteritinib armPrior sorafenibComplete remissionRemission durationOverall survivalTKI therapyTKI useSurvival outcomes
2020
Sequencing of novel agents in relapsed/refractory B‐cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia
Badar T, Szabo A, Dinner S, Liedtke M, Burkart M, Shallis RM, Yurkiewicz IR, Kuo E, Khan MA, Balasubramanian S, Yang J, Hefazi M, Podoltsev N, Patel A, Curran E, Wang A, Arslan S, Aldoss I, Siebenaller C, Mattison RJ, Litzow MR, Wadleigh M, Advani AS, Atallah E. Sequencing of novel agents in relapsed/refractory B‐cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia. Cancer 2020, 127: 1039-1048. PMID: 33259056, DOI: 10.1002/cncr.33340.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntibodies, BispecificAntineoplastic Agents, ImmunologicalDrug Administration ScheduleDrug Resistance, NeoplasmFemaleHematopoietic Stem Cell TransplantationHumansInotuzumab OzogamicinMaleMiddle AgedPrecursor Cell Lymphoblastic Leukemia-LymphomaRemission InductionRetrospective StudiesTreatment OutcomeWithholding TreatmentYoung AdultConceptsAcute lymphoblastic leukemiaRefractory B-cell acute lymphoblastic leukemiaB-cell acute lymphoblastic leukemiaMedian overall survivalINO groupNovel agentsOverall survivalLymphoblastic leukemiaComplete remissionInotuzumab ozogamicinNA therapyComparable efficacyRelapsed/refractory (r/r) B-cell acute lymphoblastic leukemiaAllogeneic hematopoietic stem cell transplantationCR/CRi rateIncomplete count recovery (CRi) ratesRefractory acute lymphoblastic leukemiaHematopoietic stem cell transplantationNovel agent therapyOutcomes of patientsStem cell transplantationBlinatumomab groupCRi rateTreatment discontinuationAdverse eventsReal-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab
Badar T, Szabo A, Advani A, Wadleigh M, Arslan S, Khan MA, Aldoss I, Siebenaller C, Schultz E, Hefazi M, Shallis RM, Yurkiewicz I, Podoltsev N, Patel AA, Curran E, Balasubramanian S, Yang J, Mattison RJ, Burkart M, Dinner S, Liedtke M, Litzow MR, Atallah E. Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab. Blood Advances 2020, 4: 2308-2316. PMID: 32453836, PMCID: PMC7252553, DOI: 10.1182/bloodadvances.2019001381.Peer-Reviewed Original ResearchConceptsMedian relapse-free survivalAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationRelapse-free survivalAcute lymphoblastic leukemiaOverall survivalCell transplantationRR diseaseClinical trialsComplete remission/complete remissionRetrospective multicenter cohort analysisB-cell acute lymphoblastic leukemiaB-cell acute lymphocytic leukemia patientsCytokine release syndromeIncomplete count recoveryMulticenter cohort analysisAcute lymphocytic leukemia patientsFavorable prognostic significanceLymphocytic leukemia patientsReal-world outcomesConsolidation therapyMRD negativityPrior therapyRelease syndromeComplete remissionReal-World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated With Inotuzumab Ozogamicin
Badar T, Szabo A, Wadleigh M, Liedtke M, Arslan S, Siebenaller C, Aldoss I, Schultz E, Hefazi M, Litzow MR, Kuo E, Wang A, Curran E, Shallis RM, Podoltsev N, Balasubramanian S, Yang J, Mattison R, Burkart M, Dinner S, Advani A, Atallah E. Real-World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated With Inotuzumab Ozogamicin. Clinical Lymphoma Myeloma & Leukemia 2020, 20: 556-560.e2. PMID: 32291234, DOI: 10.1016/j.clml.2020.03.004.Peer-Reviewed Original ResearchConceptsB-cell acute lymphocytic leukemia patientsAcute lymphocytic leukemia patientsAllo-HCTLymphocytic leukemia patientsInotuzumab ozogamicinOverall survivalLeukemia patientsAllogeneic hematopoietic stem cell transplantationMinimal residual disease negativityHematopoietic stem cell transplantationCommon grade 3Efficacy of iNOHigher adverse eventsMedian overall survivalMulticenter cohort analysisVeno-occlusive diseaseDuration of responseStem cell transplantationOverall response rateINO initiationComplete remissionMedian durationAdverse eventsMedian ageCumulative doseManagement of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study
Stahl M, Shallis RM, Wei W, Montesinos P, Lengline E, Neukirchen J, Bhatt VR, Sekeres MA, Fathi AT, Konig H, Luger S, Khan I, Roboz GJ, Cluzeau T, Martínez-Cuadron D, Raffoux E, Germing U, Umakanthan JM, Mukherjee S, Brunner AM, Miller A, McMahon CM, Ritchie EK, Rodríguez-Veiga R, Itzykson R, Boluda B, Rabian F, Tormo M, Acuña-Cruz E, Rabinovich E, Yoo B, Cano I, Podoltsev NA, Bewersdorf JP, Gore S, Zeidan AM. Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study. Leukemia 2020, 34: 3149-3160. PMID: 32132655, PMCID: PMC8155811, DOI: 10.1038/s41375-020-0783-3.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaOverall survivalMyeloid leukemiaMultivariate analysisLong-term clinical outcomesComposite complete remissionImpact of leukapheresisManagement of hyperleukocytosisMedian overall survivalThirty-day mortalityHigh-quality evidenceWhite cell countProportional hazards modelUse of leukapheresisLogistic regression modelsSignificant resource useIntensive chemotherapyComplete remissionHazard ratioClinical outcomesInferior outcomesUnadjusted analysesQuality evidencePotential complicationsOdds ratio
2019
Real World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated with Inotuzumab Ozogamicin
Badar T, Szabo A, Wadleigh M, Liedtke M, Arslan S, Siebenaller C, Aldoss I, Schultz E, Hefazi M, Litzow M, Kuo E, Wang A, Curran E, Shallis R, Podoltsev N, Balasubramanian S, Yang J, Mattison R, Burkart M, Dinner S, Advani A, Atallah E. Real World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated with Inotuzumab Ozogamicin. Blood 2019, 134: 1302. DOI: 10.1182/blood-2019-124882.Peer-Reviewed Original ResearchMedian overall survivalDuration of responseAllo-HCTOverall survivalAcute lymphocytic leukemiaTyrosine kinase inhibitorsComplete remissionB cellsInotuzumab ozogamicinAdverse eventsRefractory B-cell acute lymphocytic leukaemiaJazz PharmaceuticalsResponse rateB-cell acute lymphocytic leukemiaMinimal residual disease negativityAllogeneic stem cell transplantationAdvisory CommitteeB-cell acute lymphocytic leukemia patientsEfficacy of iNOGenentech/RocheIncomplete count recoveryMedian response durationVeno-occlusive diseaseOutcomes of patientsKaplan-Meier methodReal World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated with Blinatumomab
Badar T, Szabo A, Advani A, Wadleigh M, Arslan S, Khan M, Aldoss I, Siebenaller C, Schultz E, Hefazi M, Shallis R, Yurkiewicz I, Podoltsev N, Patel A, Curran E, Balasubramanian S, Yang J, Mattison R, Burkart M, Dinner S, Liedtke M, Litzow M, Atallah E. Real World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated with Blinatumomab. Blood 2019, 134: 3809. DOI: 10.1182/blood-2019-125466.Peer-Reviewed Original ResearchCytokine release syndromeDuration of responseMinimal residual diseaseMedian overall survivalMedian DOROverall survivalTyrosine kinase inhibitorsAllo-HCTMRD negativityComplete remissionB cellsRR diseaseClinical trialsJazz PharmaceuticalsAcute lymphocytic leukemia blastsPhiladelphia chromosome-positive diseaseAllogeneic stem cell transplantationAdvisory CommitteePositive cytotoxic T cellsB-cell acute lymphocytic leukemia patientsCR/CRiEfficacy of blinatumomabG3-4 toxicitiesGenentech/RocheIncomplete count recovery
2018
Characteristics, Treatment Patterns and Outcomes Among Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Hyperleukocytosis: Findings from a Large International Patient Cohort
Stahl M, Wei W, Montesinos P, Lengline E, Shallis R, Neukirchen J, Bhatt V, Sekeres M, Fathi A, Konig H, Luger S, Khan I, Roboz G, Cluzeau T, Martínez-Cuadron D, Raffoux E, Germing U, Umakanthan J, Mukherjee S, Brunner A, Miller A, McMahon C, Ritchie E, Rodríguez-Veiga R, Itzykson R, Boluda B, Rabian F, Tormo M, Cruz E, Rabinovich E, Yoo B, Podoltsev N, Gore S, Zeidan A. Characteristics, Treatment Patterns and Outcomes Among Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Hyperleukocytosis: Findings from a Large International Patient Cohort. Blood 2018, 132: 4040. DOI: 10.1182/blood-2018-99-112974.Peer-Reviewed Original ResearchWhite blood cell countMedian overall survivalAcute myeloid leukemiaHematopoietic stem cell transplantIntensive chemotherapyTumor lysis syndromeOverall survivalTime of presentationComplete remissionAstex PharmaceuticalsSpeakers bureauPartial remissionTreatment patternsDaiichi SankyoJazz PharmaceuticalsCleveland Clinic Taussig Cancer InstituteJanssen PharmaceuticalsMedian white blood cell countHigher white blood cell countCelgene CorporationLong-term clinical outcomesAdvisory CommitteeImpact of leukapheresisIncomplete count recoveryMDS International FoundationHypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Barnard JD, Podoltsev NA, Brunner AM, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Fathi AT, Roboz GJ, Fenaux P, Litzow MR, Perreault S, Kim TK, Prebet T, Vey N, Verma V, Germing U, Bergua JM, Serrano J, Gore SD, Zeidan AM. Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort. Blood Advances 2018, 2: 923-932. PMID: 29685952, PMCID: PMC5916007, DOI: 10.1182/bloodadvances.2018016121.Peer-Reviewed Original ResearchConceptsOverall survivalRR-AMLMedian OSOlder acute myeloid leukemia patientsAcute myeloid leukemia patientsCR/CRiIncomplete count recoveryMedian overall survivalDecreased overall survivalBone marrow blastsReasonable therapeutic optionMyeloid leukemia patientsPredictors of responseImproved response ratesLarge international patient cohortInternational patient cohortGood responseComplete remissionHematologic improvementRefractory AMLMarrow blastsMedian ageCount recoveryFrontline treatmentTherapeutic optionsAllogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Majhail N, Barnard J, Podoltsev NA, Brunner AM, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Roboz GJ, Fenaux P, Litzow M, Fathi AT, Perreault S, Kim TK, Prebet T, Vey N, Verma V, Kobbe G, Bergua J, Serrano J, Gore SD, Zeidan AM. Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study. Transplantation And Cellular Therapy 2018, 24: 1754-1758. PMID: 29649620, DOI: 10.1016/j.bbmt.2018.03.025.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationHMA therapyStem cell transplantationComplete remissionCell transplantationUnrelated hematopoietic stem cell transplantationInternational retrospective studyLimited treatment optionsAcute myeloid leukemiaChronic GVHDMedian OSPrimary refractoryRR-AMLConditioning regimenRefractory AMLPatients patientsUnrelated donorsEntire cohortPoor prognosisRetrospective studyTreatment optionsMyeloid leukemiaInternational cohortHypomethylating agent
2017
Overall survival (OS) and stem cell transplant (SCT) in patients with FLT3 mutations treated with CPX-351 versus 7+3: Subgroup analysis of a phase III study of older adults with newly diagnosed, high-risk acute myeloid leukemia (AML).
Medeiros B, Hogge D, Newell L, Bixby D, Solomon S, Strickland S, Lin T, Erba H, Powell B, Podoltsev N, Ryan R, Chiarella M, Louie A, Lancet J. Overall survival (OS) and stem cell transplant (SCT) in patients with FLT3 mutations treated with CPX-351 versus 7+3: Subgroup analysis of a phase III study of older adults with newly diagnosed, high-risk acute myeloid leukemia (AML). Journal Of Clinical Oncology 2017, 35: e18507-e18507. DOI: 10.1200/jco.2017.35.15_suppl.e18507.Peer-Reviewed Original ResearchHigh-risk acute myeloid leukemiaAcute myeloid leukemiaCPX-351Median overall survivalOverall survivalComplete remissionFLT3 mutationsDe novo acute myeloid leukemiaNovo acute myeloid leukemiaSerious adverse eventsPhase III studyPhase III trialsOverall study populationOlder ptsNeutrophil recoveryIII trialsAdverse eventsIII studyCell transplantAML patientsSafety profileStudy treatmentSubgroup analysisAML subtypesMyeloid leukemia
2016
Selecting initial treatment of acute myeloid leukaemia in older adults
Podoltsev NA, Stahl M, Zeidan AM, Gore SD. Selecting initial treatment of acute myeloid leukaemia in older adults. Blood Reviews 2016, 31: 43-62. PMID: 27745715, DOI: 10.1016/j.blre.2016.09.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaTreatment-related mortalityInduction chemotherapyComplete remissionInitial treatmentMyeloid leukemiaNovel agentsOlder adultsMedian overall survivalGroup of patientsPhase III developmentDisease-related characteristicsMechanism of actionCPX-351Overall survivalLow-intensity treatmentClinical trialsTreatment outcomesPatientsRemissionChemotherapyLeukemiaMortalityTreatmentAdults
2013
First Clinical Results Of a Randomized Phase 2 Study Of SGI-110, a Novel Subcutaneous (SQ) Hypomethylating Agent (HMA), In Adult Patients With Acute Myeloid Leukemia (AML)
Kantarjian H, Jabbour E, Yee K, Kropf P, O'Connell C, Stock W, Tibes R, Rizzieri D, Walsh K, Griffiths E, Roboz G, Savona M, Ervin T, Podoltsev N, Pemmaraju N, Daver N, Garcia-Manero G, Borthakur G, Wierda W, Ravandi F, Cortes J, Brandwein J, Odenike O, Feldman E, Chung W, Naim S, Choy G, Taverna P, Hao Y, Dimitrov G, Azab M, Issa J. First Clinical Results Of a Randomized Phase 2 Study Of SGI-110, a Novel Subcutaneous (SQ) Hypomethylating Agent (HMA), In Adult Patients With Acute Myeloid Leukemia (AML). Blood 2013, 122: 497. DOI: 10.1182/blood.v122.21.497.497.Peer-Reviewed Original ResearchAcute myeloid leukemiaPhase 2 studyTreatment of AMLRandomized phase 2 studyRefractory acute myeloid leukemiaOverall remission rateAdverse eventsComplete remissionRemission rateAstex PharmaceuticalsHypomethylating agentAML patientsSGI-110Primary endpointDose groupElderly acute myeloid leukemiaLINE-1 demethylationElderly AML patientsCommon adverse eventsComplete remission ratePhase 1 trialStem cell transplantPhase 3 investigationFirst clinical resultsECOG PS