2024
Phase I Study of Ruxolitinib in Combination with Abemaciclib for Patients with Primary or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis
Bewersdorf J, Derkach A, Zeidan A, Stein E, Mauro M, Podoltsev N, Rampal R. Phase I Study of Ruxolitinib in Combination with Abemaciclib for Patients with Primary or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis. Blood 2024, 144: 6659-6659. DOI: 10.1182/blood-2024-194918.Peer-Reviewed Original ResearchDose-limiting toxicityCancer Institute Common Terminology Criteria for Adverse EventsTreatment-related adverse eventsAdverse eventsDose levelsCombination therapySpleen volumeInhibitor abemaciclibGrade 3Patients discontinued treatment due to adverse eventsNational Cancer Institute Common Terminology Criteria for Adverse EventsPhase I dose-escalation trialTreatment due to adverse eventsCommon Terminology Criteria for Adverse EventsDisease progressionRecommended phase II doseMulticenter Phase IPlanned dose levelsGrade 3 thrombocytopeniaMedian overall survivalPhase II doseBone marrow blastsBone marrow fibrosisClinically significant bleedingData cut-offZiftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007
Zeidan A, Wang E, Issa G, Erba H, Altman J, Balasubramanian S, Strickland S, Roboz G, Schiller G, McMahon C, Palmisiano N, Madanat Y, Rotta M, Nadiminti K, Wei H, Riches M, Corum D, Leoni M, Dale S, Fathi A. Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007. Blood 2024, 144: 214-214. DOI: 10.1182/blood-2024-198218.Peer-Reviewed Original ResearchDose-limiting toxicityMinimal residual diseaseAcute myeloid leukemiaMedian time to neutrophil recoveryDays to platelet recoveryMinimal residual disease negativityDecreased neutrophil countKMT2A-rDecreased platelet countNPM1 mutationsAdverse eventsCRC ratesDose levelsNeutrophil recoveryData cutoffQTc prolongationPlatelet recoveryPlatelet countMyeloid leukemiaNeutrophil countDifferentiation syndromeClinical activityCycle 1 day 8Persistent acute myeloid leukemiaStandard dose of cytarabineZiftomenib Combined with Venetoclax/Azacitidine in Relapsed/Refractory NPM1 -m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007
Fathi A, Issa G, Wang E, Erba H, Altman J, Balasubramanian S, Roboz G, Schiller G, McMahon C, Palmisiano N, Juckett M, Madanat Y, Rotta M, Pratz K, Yaghmour G, Nadiminti K, Wei H, Riches M, Corum D, Leoni M, Dale S, Zeidan A. Ziftomenib Combined with Venetoclax/Azacitidine in Relapsed/Refractory NPM1 -m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007. Blood 2024, 144: 2880-2880. DOI: 10.1182/blood-2024-199170.Peer-Reviewed Original ResearchAcute myeloid leukemiaDecreased neutrophil countDecreased platelet countNPM1 mutationsKMT2A-rAdverse eventsCRC ratesClinical activityR/R patientsData cutoffQTc prolongationPlatelet countMyeloid leukemiaNucleophosmin 1Neutrophil countDifferentiation syndromeComposite complete remission rateCycle 1 day 8R/R acute myeloid leukemiaTreatment-emergent adverse eventsDose of venetoclaxInhibitor-naive patientsDose-escalation cohortsDose-expansion phaseComplete remission rateTrial in Progress: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination with Azacitidine in Patients with Newly Diagnosed Higher-Risk Myelodysplastic Syndromes (AK117-205)
Zeidan A, Tong H, Xiao Z, Baratam P, Abboud R, Benton C, Zeidner J, Borate U, Chai-Ho W, Lu Y, Yang J, Hu M, Li B, Xia M, Sallman D. Trial in Progress: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination with Azacitidine in Patients with Newly Diagnosed Higher-Risk Myelodysplastic Syndromes (AK117-205). Blood 2024, 144: 6705-6705. DOI: 10.1182/blood-2024-200541.Peer-Reviewed Original ResearchAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEastern Cooperative Oncology GroupIPSS-R scoreEvent-free survivalStem cell transplantationAcute myeloid leukemiaOverall survivalIPSS-RTransfusion independenceComplete responseCR rateDouble-blindCell transplantationHR-MDSMyeloproliferative neoplasmsAdverse eventsChimeric antigen receptor T cellsTransformation to acute myeloid leukemiaAnemia ratesMulticenter phase 2 studyTreated with hypomethylating agentsHigher-risk myelodysplastic syndromesSeverity of adverse eventsAdequate organ functionRenew Trial in Progress: A Phase 3, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER-050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Neoplasms (MDS)
Komrokji R, Diez-Campelo M, Chee L, Cluzeau T, DeZern A, Fenaux P, Garcia-Manero G, Giagounidis A, Platzbecker U, Della Porta M, Santini V, Sekeres M, Zeidan A, Buckstein R, Ross M, Jiang Y, Bobba S, Hankin M, Materna C, Graham C, Thamake S, Rovaldi C, Grayson D, Salstrom J. Renew Trial in Progress: A Phase 3, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER-050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Neoplasms (MDS). Blood 2024, 144: 3228.1-3228.1. DOI: 10.1182/blood-2024-200797.Peer-Reviewed Original ResearchDurability of responseMyelodysplastic neoplasmsFollow-up periodTransfusion burdenProportion of participantsAdverse eventsTransfusion independenceIneffective hematopoiesisDouble-blindPlacebo-controlled phase 3 studyAchievement of transfusion independenceMultiple stages of hematopoiesisSafety follow-up periodDouble-blind treatment periodLong-term follow-up periodSeverity of adverse eventsLong-term follow-upErythroid maturation agentLow transfusion burdenSustained hematologic improvementTreatment of transfusion-dependent anemiaPlacebo-controlled studyTransfusion-dependent anemiaPhase 3 studyProgression to AMLResults from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN)
Garcia-Manero G, McCloskey J, Scott B, Griffiths E, Kiner-Strachan B, Brunner A, Zeidan A, Traer E, Madanat Y, Meyer J, Erba H, Baratam P, Borate U, Sano Y, Oganesian A, Zhu L, Keer H, Savona M. Results from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN). Blood 2024, 144: 662. DOI: 10.1182/blood-2024-203569.Peer-Reviewed Original ResearchDose-limiting toxicityPhase 1 trialDose-expansion partMDS/MPN overlap syndromesMyelodysplastic syndromeAdverse eventsDose combinationMDS/myeloproliferative neoplasmImmediate-releaseOverlap syndromeAUC exposureOpen-label phase 1 trialDelayed-releaseCytidine deaminaseProlonged grade 4 neutropeniaIncreased absolute bioavailabilityMarrow complete responsePhase 2 doseGrade 4 neutropeniaDose-escalation partErythropoiesis-stimulating agentsAcute myeloid leukemiaTreatment of patientsClinical efficacy assessmentDNA methyltransferase inhibitorLuspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial
Della Porta M, Garcia-Manero G, Santini V, Zeidan A, Komrokji R, Shortt J, Valcárcel D, Jonasova A, Dimicoli-Salazar S, Tiong I, Lin C, Li J, Zhang J, Pilot R, Kreitz S, Pozharskaya V, Keeperman K, Rose S, Prebet T, Lai Y, Degulys A, Paolini S, Cluzeau T, Fenaux P, Platzbecker U. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. The Lancet Haematology 2024, 11: e646-e658. PMID: 39038479, DOI: 10.1016/s2352-3026(24)00203-5.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesRed blood cell transfusion independenceTreatment-emergent adverse eventsMedian follow-upEpoetin alfa groupMyelodysplastic syndromeLuspatercept groupTransfusion-dependentSerum erythropoietin concentrationPrimary endpointEpoetin alfaTransfusion independenceOpen-labelAlfa groupAdverse eventsFollow-upRed blood cell transfusion burdenErythropoietin concentrationIntention-to-treat populationControlled trialsCommon grade 3Epoetin alfa recipientsMean haemoglobin increasePrimary analysisProportion of patientsEfficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge.
Zeidan A, Santini V, Platzbecker U, Sekeres M, Savona M, Fenaux P, Madanat Y, Raza A, Xia Q, Sun L, Riggs J, Shah S, Navada S, Berry T, Komrokji R. Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge. Journal Of Clinical Oncology 2024, 42: 6566-6566. DOI: 10.1200/jco.2024.42.16_suppl.6566.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesRBC-TIMyeloid growth factorsPlatelet transfusionsTransfusion-dependentHb levelsGrowth factorGrowth factor supportLong-term respondersGrowth factor useErythropoiesis stimulating agentsHb riseSevere neutropeniaMyelodysplastic syndromePlacebo groupPrimary endpointSecondary endpointsFactor supportInvestigator's discretionClinical benefitAdverse eventsPlaceboAnalysis cutoffImetelstatDisease progressionOral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Deeg H, Patel P, Sabloff M, Keating M, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao K, Oganesian A, Hao Y, Keer H, Azab M, Savona M. Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. The Lancet Haematology 2024, 11: e15-e26. PMID: 38135371, DOI: 10.1016/s2352-3026(23)00338-1.Peer-Reviewed Original ResearchConceptsChronic myelomonocytic leukemiaIntravenous decitabineMyelodysplastic syndromeMyelomonocytic leukemiaOral therapyPrimary endpointAdverse eventsEastern Cooperative Oncology Group performance status 0Treatment cyclesCycle 1Full treatment dosePerformance status 0Treatment-related deathsFrequent adverse eventsSerious adverse eventsPhase 3 studyPhase 3 trialPotential treatment benefitsCommunity-based clinicsAcute myeloid leukemiaNext treatment cycleTreatment of individualsOral decitabineStatus 0Treatment discontinuationEFFICACY AND SAFETY OF LUSPATERCEPT VERSUS EPOETIN ALFA IN ERYTHROPOIESIS-STIMULATING AGENT (ESA)-NAIVE PATIENTS WITH TRANSFUSION-DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS): FULL ANALYSIS OF THE COMMANDS TRIAL
Garcia-Manero G, Platzbecker U, Santini V, Zeidan A, Fenaux P, Komrokji R, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong I, Lin C, Li J, Zhang J, Giuseppi A, Kreitz S, Pozharskaya V, Keeperman K, Rose S, Prebet T, Degulys A, Paolini S, Cluzeau T, Della Porta M. EFFICACY AND SAFETY OF LUSPATERCEPT VERSUS EPOETIN ALFA IN ERYTHROPOIESIS-STIMULATING AGENT (ESA)-NAIVE PATIENTS WITH TRANSFUSION-DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS): FULL ANALYSIS OF THE COMMANDS TRIAL. Leukemia Research Reports 2024, 21: 100447. DOI: 10.1016/j.lrr.2024.100447.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesTreatment-emergent adverse eventsEA-treated patientsRBC-TIPrimary endpointHI-ERed blood cell transfusion independenceHematological improvement-erythroidTransfusion independenceErythroid responseMyelodysplastic syndromeSecondary endpointsAdverse eventsFull analysisLuspaterceptAssessed efficacySafety resultsEpoetin alfaTreatment durationPatientsEndpointEfficacyDurationPost-treatmentAML
2023
Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial
Zeidan A, Ando K, Rauzy O, Turgut M, Wang M, Cairoli R, Hou H, Kwong Y, Arnan M, Meers S, Pullarkat V, Santini V, Malek K, Kiertsman F, Niolat J, Ramos P, Menssen H, Fenaux P, Miyazaki Y, Platzbecker U. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Haematology 2023, 11: e38-e50. PMID: 38065203, DOI: 10.1016/s2352-3026(23)00333-2.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeProgression-free survivalComplete response rateMyelodysplastic syndromePlacebo groupPrimary endpointUntreated patientsAdverse eventsComplete responseResponse rateImmune-mediated adverse eventsMedian progression-free survivalRandomised phase 3 trialT-cell immunoglobulin domainFinal data cutoffTreatment-related deathsCommon adverse eventsFull analysis setMucin domain 3Phase 2 studyPhase 2 trialPhase 3 trialLeukaemic stem cellsFebrile neutropeniaData cutoffImetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial
Platzbecker U, Santini V, Fenaux P, Sekeres M, Savona M, Madanat Y, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman L, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji R, Zeidan A. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 2023, 403: 249-260. PMID: 38048786, DOI: 10.1016/s0140-6736(23)01724-5.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsPlacebo groupAdverse eventsMyelodysplastic syndromeGrade 3Subsequent anti-cancer therapyTreatment-emergent adverse eventsTreatment-emergent grade 3Days of randomisationIPSS risk groupRBC transfusion burdenTransfusion independence rateTreatment-related deathsUnacceptable toxic effectsPlacebo-controlled trialDisease-modifying activityPhase 2 trialPhase 3 trialPrimary efficacy analysisProportion of patientsWithdrawal of consentUnmet medical needComputer-generated scheduleAnti-cancer therapyA 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 efficacyBlinatumomab in Combination with Immune Checkpoint Inhibitors (ICIs) of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Results of a Phase I Study
Webster J, Luskin M, Rimando J, Blackford A, Zeidan A, Sharon E, Streicher H, DeAngelo D, Luznik L, Gojo I. Blinatumomab in Combination with Immune Checkpoint Inhibitors (ICIs) of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Results of a Phase I Study. Blood 2023, 142: 966. DOI: 10.1182/blood-2023-191109.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsMixed phenotype acute leukemiaRelapse-free survivalOverall survivalAcute lymphoblastic leukemiaComplete remissionPD-1Checkpoint inhibitorsExtramedullary diseaseAdverse eventsBM blastsGrade 3Positive B-cell acute lymphoblastic leukemiaResponse rateImmune-related adverse eventsB-cell acute lymphoblastic leukemiaMulti-center phase IPhase IDose-escalation schemaNon-hematologic toxicitiesMedian overall survivalDose-escalation studyPD-L1 expressionDuration of responseT cell subpopulationsEncouraging Efficacy Observed in Bexmab Study: A Phase 1/2 Study to Assess Safety and Efficacy of Bexmarilimab in Combination with Standard of Care in Myeloid Malignancies
Kontro M, Stein A, Pyörälä M, Rimpiläinen J, Siitonen T, Hollmén M, Fjaellskog M, Pawlitzky I, Zeidan A, Daver N. Encouraging Efficacy Observed in Bexmab Study: A Phase 1/2 Study to Assess Safety and Efficacy of Bexmarilimab in Combination with Standard of Care in Myeloid Malignancies. Blood 2023, 142: 2915. DOI: 10.1182/blood-2023-174912.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AMLCLEVER-1Complete remissionStandard of careBex treatmentAdverse eventsBone marrow cellsHMA failureMarrow CRPatient BMPrior therapyPartial remissionAML patientsMedian numberT cellsDose levelsMyeloid malignanciesHigh-risk MDS patientsMarrow cellsMarrow complete remissionR AML patientsRisk MDS patientsNK cell numbersPhase 1/2 studyDurable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)
Platzbecker U, Komrokji R, Zeidan A, Fenaux P, Sekeres M, Savona M, Madanat Y, Jonášová A, Illmer T, Sherman L, Berry T, Riggs J, Xia Q, Navada S, Wan Y, Huang F, Feller F, Santini V. Durable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs). Blood 2023, 142: 4605. DOI: 10.1182/blood-2023-181154.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis stimulating agentsPhase 3 trialTransfusion independenceVariant allele frequencyEnd pointTransfusion burdenAdverse eventsRed blood cell transfusionExploratory end pointsFrequent adverse eventsPrimary end pointRBC transfusion burdenReversible grade 3Secondary end pointsBlood cell transfusionDisease-modifying activityKaplan-Meier methodDuration of responseLoss of responseAdditional baseline characteristicsHigh telomerase activityCell transfusionBaseline characteristicsClinical responseSabatolimab in Combination with Hypomethylating Agents (HMAs) Was Safe in Patients (Pts) with Intermediate-, High-, or Very-High-Risk Myelodysplastic Syndrome (MDS)
Garcia-Manero G, Lyons R, Nandal S, Ashraf M, Thellaboina R, Ruckel-Kumar J, Menssen H, Zeidan A. Sabatolimab in Combination with Hypomethylating Agents (HMAs) Was Safe in Patients (Pts) with Intermediate-, High-, or Very-High-Risk Myelodysplastic Syndrome (MDS). Blood 2023, 142: 4606. DOI: 10.1182/blood-2023-186490.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeAdverse eventsHematologic improvementPartial remissionMyelodysplastic syndromeHypomethylating agentMarrow CRInterim analysisStable diseaseData cutoffLast doseInternational Prognostic Scoring System criteriaResponse rateCount decreaseCycle 1 day 1Second-line treatment optionExtension phaseHematologic adverse eventsNeutrophil count decreaseOral hypomethylating agentPhase Ib studySerious adverse eventsFatal adverse eventsMonths of treatmentSingle-arm studyEfficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial
Platzbecker U, Della Porta M, Santini V, Zeidan A, Komrokji R, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong I, Lin C, Li J, Zhang J, Giuseppi A, Kreitz S, Pozharskaya V, Keeperman K, Rose S, Shetty J, Hayati S, Vodala S, Prebet T, Degulys A, Paolini S, Cluzeau T, Fenaux P, Garcia-Manero G. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. The Lancet 2023, 402: 373-385. PMID: 37311468, DOI: 10.1016/s0140-6736(23)00874-7.Peer-Reviewed Original ResearchConceptsLower-risk myelodysplastic syndromesRed blood cell transfusion independenceEpoetin alfa groupErythropoiesis-stimulating agentsEpoetin alfaMyelodysplastic syndromeInterim analysisPrimary endpointAdverse eventsAlfa groupTransfusion independenceLower riskBody weightTreatment-emergent adverse eventsTreatment-related adverse eventsRed blood cell transfusionDurable clinical efficacyMean hemoglobin increaseMedian treatment exposureBlood cell transfusionCOVID-19 pneumoniaSubgroup of patientsWeeks of treatmentTreatment of anemiaAcute myeloid leukemiaPhase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies
Patel M, Donnellan W, Byrne M, Asch A, Zeidan A, Baer M, Fathi A, Kuykendall A, Zheng F, Walker C, Cheng L, Marando C, Savona M. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clinical Lymphoma Myeloma & Leukemia 2023, 23: 674-686. PMID: 37290996, DOI: 10.1016/j.clml.2023.05.002.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsDose-limiting toxicityAdvanced hematologic malignanciesAcute myeloid leukemiaMyelodysplastic syndromeHematologic malignanciesCare agentsHigh-risk myelodysplastic syndromeMDS/myeloproliferative neoplasmPhase 1/2 studyEffective combination strategiesAdverse eventsComplete responseLymphoproliferative neoplasmsWeek 12Multiple myelomaSpleen volumeAcute leukemiaMyeloid leukemiaPreclinical modelsPatientsMyeloproliferative neoplasmsMoloney murine leukemia virus (PIM) kinasesMyelofibrosisKinase inhibitors
2022
A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes
Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng W, Zhou Y, Hoffman D, Harb JG, Potluri J, Garcia‐Manero G. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American Journal Of Hematology 2022, 98: 272-281. PMID: 36309981, PMCID: PMC10100228, DOI: 10.1002/ajh.26771.Peer-Reviewed Original ResearchConceptsMedian overall survivalMyelodysplastic syndromeOverall survivalTransfusion independenceHematological improvementTherapy failureHigh-risk myelodysplastic syndromeInternational Working Group criteriaHematological adverse eventsPhase 1b studyRefractory myelodysplastic syndromeStandard of careEfficacy of venetoclaxEffective therapeutic strategyFebrile neutropeniaMarrow CROral venetoclaxComplete remissionAdverse eventsMedian durationAzacitidine treatmentMedian timeMarrow responseMulticenter studyGroup criteria