2022
Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors. Leukemia & Lymphoma 2022, 64: 188-196. PMID: 36287540, PMCID: PMC9905301, DOI: 10.1080/10428194.2022.2136952.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSalvage therapyIDH1/2 inhibitorsIDH2 inhibitorsMyeloid leukemiaResponse rateRefractory acute myeloid leukemiaEffective salvage therapyLow-dose cytarabineMedian overall survivalRetrospective cohort studyOverall response rateLow response rateCohort studyOverall survivalAML patientsTreatment optionsFLT3 inhibitorsITD mutationPatientsTherapyFLT3Little dataVenetoclaxInhibitors
2021
Outcomes for Patients with Late-Stage Mutant-IDH2 (m IDH2) Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Treated with Enasidenib Vs Other Lower-Intensity Therapies in the Randomized, Phase 3 IDHentify Trial
DiNardo C, Montesinos P, Schuh A, Papayannidis C, Vyas P, Wei A, Zeidan A, Bluemmert I, Yu X, Hasan M, Martin-Regueira P, de Botton S. Outcomes for Patients with Late-Stage Mutant-IDH2 (m IDH2) Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Treated with Enasidenib Vs Other Lower-Intensity Therapies in the Randomized, Phase 3 IDHentify Trial. Blood 2021, 138: 1243. DOI: 10.1182/blood-2021-147593.Peer-Reviewed Original ResearchClinical Trials CommitteeBest supportive careEvent-free survivalBristol-Myers SquibbIntermediate-dose cytarabineMedian overall survivalR AMLOverall survivalHematologic improvementTransfusion independenceTrials CommitteeCurrent equity holderSpeakers bureauDaiichi SankyoRefractory acute myeloid leukemiaAdvisory CommitteeAdverse-risk AMLConventional care regimensLow-dose cytarabineMedian age overallPrimary refractory AMLStudy drug doseOpen-label trialLow-intensity therapyOverall response rate
2020
A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Zeidan AM, Ridinger M, Lin TL, Becker PS, Schiller GJ, Patel PA, Spira AI, Tsai ML, Samuëlsz E, Silberman SL, Erlander M, Wang ES. A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clinical Cancer Research 2020, 26: 6132-6140. PMID: 32998961, DOI: 10.1158/1078-0432.ccr-20-2586.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDecitabineDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLeukemia, Myeloid, AcuteMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalPiperazinesPrognosisPyrazolesQuinazolinesSalvage TherapyConceptsAcute myeloid leukemiaPhase Ib studyMyeloid leukemiaIb studyRefractory (R/R) AMLFirst-cycle dose-limiting toxicitiesRefractory acute myeloid leukemiaOngoing phase II trialAntileukemic activityMost grade 3Low-dose cytarabinePhase II trialBone marrow blastsDose-limiting toxicityPLK1 inhibitorsPolo-like kinase 1Evaluable patientsExploratory endpointsComplete remissionII trialPrimary endpointAdverse eventsClinical responseMarrow blastsCount recoveryGlasdegib in combination with azacitidine (AZA) in patients (pts) with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML): Effects on marrow recovery and transfusion independence.
Zeidan A, Schuster M, Joris M, Krauter J, Maertens J, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang E, Ma W, Zeremski M, Kudla A, Chan G, Sekeres M. Glasdegib in combination with azacitidine (AZA) in patients (pts) with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML): Effects on marrow recovery and transfusion independence. Journal Of Clinical Oncology 2020, 38: 7526-7526. DOI: 10.1200/jco.2020.38.15_suppl.7526.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaAcute myeloid leukemiaAbsolute neutrophil countMyelodysplastic syndromeEarly hematopoietic recoveryIntensive chemotherapyMedian durationTransfusion independenceMarrow recoveryHematopoietic recoveryPlatelet recoveryHigh-risk myelodysplastic syndromeEarly marrow recoveryEarly platelet recoveryManageable safety profilePhase Ib studyUp-front treatmentLow-dose cytarabineDose delaysPartial remissionRemission rateNeutrophil countOverall survivalOral inhibitorSafety profile
2019
A Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia
Sekeres M, Schuster M, Joris M, Krauter J, Maertens J, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang E, Wendy W, Zeremski M, Kudla A, Chan G, Zeidan A. A Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia. Blood 2019, 134: 177. DOI: 10.1182/blood-2019-124050.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaAcute myeloid leukemiaLow-dose cytarabineMedian treatment durationComplete remissionPhase 1b trialIntensive chemotherapyOverall survivalMyelodysplastic syndromePersonal feesAdverse eventsMyelomonocytic leukemiaSpeakers bureauSerious TEAEsFebrile neutropeniaMedian ageMedian timeEuropean LeukemiaNetRisk categoriesMyeloid leukemiaMedian (95% CI) OSMortality rateTreatment durationCR/complete remissionSafety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Zeidan A, Schiller G, Lin T, Becker P, Patel P, Wang E, Spira A, Tsai M, Ridinger M, Croucher P, Erlander M, Silberman S. Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 230. DOI: 10.1182/blood-2019-126262.Peer-Reviewed Original ResearchPositive ptsBiomarker positivityPhase 1bBristol-Myers SquibbSpeakers bureauObjective responseCount recoveryPreliminary efficacyBlood samplesNegative groupRelapsed/Refractory Acute Myeloid LeukemiaADC therapeuticsDay 1Jazz PharmaceuticalsRefractory acute myeloid leukemiaBoehringer IngelheimDaiichi SankyoIncomplete count recoveryPhase 1b/2 studyPreclinical AML modelsSubset of ptsLow-dose cytarabinePredictive gene expression signaturesDose-escalation trialPlatelet count recoveryClinical Benefit of Glasdegib in Combination with Azacitidine or Low-Dose Cytarabine in Patients with Acute Myeloid Leukemia
Zeidan A, Schuster M, Krauter J, Maertens J, Gyan E, Joris M, Menne T, Vyas P, Wendy W, O'Connell A, Zeremski M, Kudla A, Chan G, Sekeres M. Clinical Benefit of Glasdegib in Combination with Azacitidine or Low-Dose Cytarabine in Patients with Acute Myeloid Leukemia. Blood 2019, 134: 3916. DOI: 10.1182/blood-2019-124034.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAcute myeloid leukemiaLow-dose cytarabineMedian treatment durationIntensive chemotherapyOverall survivalPersonal feesMyelodysplastic syndromeDose delaysSpeakers bureauMedian followMyeloid leukemiaTreatment durationSerious treatment-emergent adverse eventsRandomized phase 3 trialMonths median overall survivalNon-financial supportAdvisory CommitteeSeattle GeneticsDaiichi SankyoIncomplete hematologic recoveryOlder unfit patientsMedian overall survivalSuperior overall survivalAbsolute neutrophil count1066O Polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with low-dose cytarabine or decitabine in patients with relapsed/refractory acute myeloid leukaemia in phase Ib
Zeidan A, Becker P, Patel P, Schiller G, Tsai M, Lin T, Wang E, Erlander M, Cortes J. 1066O Polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with low-dose cytarabine or decitabine in patients with relapsed/refractory acute myeloid leukaemia in phase Ib. Annals Of Oncology 2019, 30: v435. DOI: 10.1093/annonc/mdz251.001.Peer-Reviewed Original ResearchTarget engagementEvaluable ptsHigh dosesRefractory acute myeloid leukemiaInhibition of PLK1CR/CRiLow-dose cytarabinePreclinical AML modelsR AML patientsDose-escalation phasePolo-like kinase 1Anti-leukaemic activityAcute myeloid leukemiaEvaluable patientsLDAC armBM blastsDose escalationAML patientsPolo-like kinase 1 inhibitorsEscalation phaseBiomarker statusMyeloid leukemiaSelective PLK1 inhibitorBlood samplesHigh dose
2018
Preliminary Safety, Pharmacokinetics (PK) and Pharmacodynamic (PD) Analysis of the Polo-like Kinase-1 (PLK1) Inhibitor PCM-075, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (D) in Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)
Zeidan A, Schiller G, Spira A, Patel P, Tsai M, Ridinger M, Silberman S, Erlander M, Cortes J. Preliminary Safety, Pharmacokinetics (PK) and Pharmacodynamic (PD) Analysis of the Polo-like Kinase-1 (PLK1) Inhibitor PCM-075, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (D) in Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML). Blood 2018, 132: 4043. DOI: 10.1182/blood-2018-99-112590.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AMLPhase 1 trialAdverse eventsPLK1 inhibitionBlast cellsPK profilesNon-hematologic adverse eventsPrevious phase 1 trialRandomized phase 2 studyStandard dose-escalation designRefractory acute myeloid leukemiaBM blast cellsGrade 1 fatigueGrade 1 nauseaPreclinical AML modelsTreatment-related deathsLow-dose cytarabinePhase 2 studySerious adverse eventsSpeakers bureauDose-escalation trialFurther dose escalationPhase 3 studyDose-escalation designOutcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database
Shallis R, Stahl M, Wei W, Montesinos P, Lengline E, 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, Podoltsev N, Gore S, Zeidan A. Outcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database. Blood 2018, 132: 3999. DOI: 10.1182/blood-2018-99-119755.Peer-Reviewed Original ResearchTumor lysis syndromeIntensive chemotherapyIntensive care unitOverall survivalClinical evidenceAstex PharmaceuticalsSpeakers bureauDaiichi SankyoMedian OSWorse OSAML patientsPlatelet countEastern Cooperative Oncology Group performance statusJazz PharmaceuticalsCleveland Clinic Taussig Cancer InstituteJanssen PharmaceuticalsOne-year OS probabilityCelgene CorporationAdvisory CommitteeMDS International FoundationPoor-risk AMLBest supportive careLow-dose cytarabineMedian overall survivalOutcomes of patients