A review of the isocitrate dehydrogenase inhibitors in management of adult patients with AML and MDS
Norman M, Yamartino K, Gerstein R, Shallis R, Mendez L, Podoltsev N, Stahl M, Eighmy W, Zeidan A. A review of the isocitrate dehydrogenase inhibitors in management of adult patients with AML and MDS. Expert Review Of Hematology 2024, 17: 755-767. PMID: 39474840, DOI: 10.1080/17474086.2024.2422554.Peer-Reviewed Original ResearchDiagnosed AMLSurvival benefitManagement of acute myeloid leukemiaDevelopment of oral therapiesIsocitrate dehydrogenase inhibitorsNewly diagnosed AMLManagement of adult patientsPost-transplant maintenanceAcute myeloid leukemiaSingle-arm studyExcellent response ratesIDH inhibitorsRelapsed AMLHypomethylating agentsInhibitor therapyMyelodysplastic syndromeOral therapyCombination therapyPost-transplantMyeloid leukemiaImproved survivalSingle-armAdult patientsAzacitidineRandomized studyValidation of Recent Response Criteria (ELN-22, IWG-23 and PB-CR) in 1634 MDS/CMML/AML Patients Treated with HMA or HMA-Ven Using CPH Models and a CPH Deep Neural Network - Can or Should Response Criteria be Harmonized for Similarly Treated Patients?
Pleyer L, Vaisband M, Klammer P, Drost M, Angermann H, Keil F, Petzer V, Heibl S, Moritz J, Girschikofsky M, Stampfl-Mattersberger M, Pichler A, Hartmann B, Aschauer G, Schmitt C, Vallet S, Boros S, Pichler P, Hammerl-Steiner A, Renneberg F, Majjiga D, Russ G, Egle A, Leisch M, Melchardt T, Zaborsky N, Faber V, Bewersdorf J, Zeidan A, Hasenauer J, Greil R. Validation of Recent Response Criteria (ELN-22, IWG-23 and PB-CR) in 1634 MDS/CMML/AML Patients Treated with HMA or HMA-Ven Using CPH Models and a CPH Deep Neural Network - Can or Should Response Criteria be Harmonized for Similarly Treated Patients? Blood 2024, 144: 7511-7511. DOI: 10.1182/blood-2024-208073.Peer-Reviewed Original ResearchComposite complete remissionTime to next treatmentCox proportional hazardsHypomethylating agentsOverall survivalCox proportional hazards modelsMedian OSResponse CriteriaTreated ptsCycles of HMAHigher-risk MDSKaplan-Meier methodBone marrow evaluationProspective cohort studyStandard of careComplete remissionMarrow evaluationTreated patientsMultivariable adjustmentNext treatmentCohort studyClinical trialsClinical overlapHazard ratioDisease entityClinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database
Getz T, Kewan T, Bewersdorf J, Stempel J, Lanino L, Wei W, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, McMahon C, Shallis R, Zeidner J, Savona M, Ball S, Chandhok N, Logothetis C, Bidikian A, Roboz G, Rolles B, Wang E, Harris A, Amaya M, Hawkins H, Grenet J, Xie Z, Madanat Y, Abaza Y, Badar T, Haferlach T, Maciejewski J, Sallman D, Enjeti A, Al-Rabi K, Halahleh K, Hiwase D, Diez-Campelo M, Valcarcel D, Haferlach C, Pleyer L, Kotsianidis I, Pappa V, Santini V, Consagra A, Al-Kali A, Ogawa S, Nannya Y, Stahl M, Della Porta M, Komrokji R, Zeidan A. Clinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database. Blood 2024, 144: 3219-3219. DOI: 10.1182/blood-2024-202075.Peer-Reviewed Original ResearchNon-complex karyotypeInternational Prognostic Scoring SystemCytogenetic risk groupHMA initiationComplex karyotypeIPSS-RHypomethylating agentsOverall survivalRisk groupsCytogenetic abnormalitiesAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationAssociated with worse survivalHypomethylating agent combinationsPoor-risk cytogeneticsPeripheral blood blastsTreated with azacitidinePrognostic Scoring SystemMeasured overall survivalStem cell transplantationKaplan-Meier methodLog-rank testOutcomes of PTTime-to-event analysisRisk of patientsOral Decitabine/Cedazuridine in Patients with MDS and TP53 Mutations: A Propensity Score Matching Analysis from the Phase II and III Trials
Urrutia S, Sasaki K, Bataller A, Kantarjian H, Montalban-Bravo G, McCloskey J, Griffiths E, Yee K, Zeidan A, Savona M, Oganesian A, Sano Y, Keer H, Garcia-Manero G. Oral Decitabine/Cedazuridine in Patients with MDS and TP53 Mutations: A Propensity Score Matching Analysis from the Phase II and III Trials. Blood 2024, 144: 661-661. DOI: 10.1182/blood-2024-193274.Peer-Reviewed Original ResearchMedian overall survivalHematopoietic stem cell transplantationHypomethylating agentsTP53 mutationsOverall survivalImproved survivalMedian follow-up timeIPSS-R scoreComplete response rateStem cell transplantationECOG performance statusPropensity score matching analysisFollow-up timeScore matching analysisIPSS-RComplex cytogeneticsCell transplantationPerformance statusDecitabine/cedazuridineTP53wtCo-mutationsLandmark analysisPoor outcomeTP53mutMedian numberLandscape of Immune Cell States and Ecosystems in Patients with Myelodysplastic Syndrome to Refine Prognostic Assessment and Predict Treatment Response. a Study By i4MDS Consortium
Riva E, Calvi M, Zampini M, Dall'Olio L, Merlotti A, Russo A, Maggioni G, Orlandi L, Frigo A, Ficara F, Crisafulli L, Sauta E, D'Amico S, Lugli E, Campagna A, Ubezio M, Tentori C, Todisco G, Lanino L, Buizza A, Ventura D, Pinocchio N, Saba E, Santoro A, Santini V, van de Loosdrecht A, Komrokji R, Garcia-Manero G, Fenaux P, Ades L, Platzbecker U, Haferlach T, Almeida A, Zeidan A, Kordasti S, Remondini D, Castellani G, Di Vito C, Mavilio D, Della Porta M. Landscape of Immune Cell States and Ecosystems in Patients with Myelodysplastic Syndrome to Refine Prognostic Assessment and Predict Treatment Response. a Study By i4MDS Consortium. Blood 2024, 144: 665-665. DOI: 10.1182/blood-2024-200184.Peer-Reviewed Original ResearchMyelodysplastic syndromeImmune dysfunctionClinical work-upIPSS-MHypomethylating agentsBone marrowImmune ecosystemNatural killerNK cellsImmune monitoringPeripheral bloodT cellsAntibody panelClinical heterogeneity of myelodysplastic syndromesPatients treated with hypomethylating agentsCohort of MDS patientsLevel of immune dysfunctionRisk of leukemic transformationResponse to hypomethylating agentsHeterogeneity of myelodysplastic syndromesMulti-color flow cytometryWork-up of patientsClinical work-up of patientsImmune monitoring approachesMDS microenvironmentInitial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents
Komrokji R, Santini V, Platzbecker U, Van Eygen K, Diez-Campelo M, De Paz R, Sanz G, Thépot S, Kaźmierczak M, Oliva E, Sekeres M, Fenaux P, Madanat Y, Savona M, Riggs J, Dougherty S, Lennox A, Xia Q, Sun L, Berry T, Zeidan A. Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents. Blood 2024, 144: 4590-4590. DOI: 10.1182/blood-2024-200885.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsHematological improvement-erythroidFood and Drug AdministrationRBC-TIPhase 3 trialPlacebo recipientsHypomethylating agentsInternational Working GroupData cutoffMyelodysplastic syndromeTransfusion reductionRed blood cellsProarrhythmic riskProgression to acute myeloid leukemiaErythropoiesis-stimulating agent useConcentration-QT relationshipEffects of imetelstatRBC transfusion independenceGrade 3/4 neutropeniaMedian treatment durationKaplan-Meier methodologyClinically meaningful efficacyUnited States Food and Drug AdministrationAcute myeloid leukemiaEffect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes
Platzbecker U, Santini V, Zeidan A, Sekeres M, Fenaux P, Raza A, Mittelman M, Thépot S, Buckstein R, Germing U, Madanat Y, Diez-Campelo M, Valcarcel D, Jonasova A, Dougherty S, Shah S, Xia Q, Sun L, Navada S, Savona M, Komrokji R. Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes. Blood 2024, 144: 352-352. DOI: 10.1182/blood-2024-203612.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesHematological improvement-erythroidErythropoiesis-stimulating agentsErythropoiesis-stimulating agent therapyHb riseRBC-TIHypomethylating agentsTransfusion reductionClinical activityMyelodysplastic syndromeQTc studyRed blood cellsPrior treatmentInternational Working GroupRBC transfusion independenceHypomethylating agent treatmentTransfusion-dependent patientsPhase 2/3 trialsLimited treatment optionsUnited States Food and Drug AdministrationStates Food and Drug AdministrationFirst-in-classFood and Drug AdministrationRBC-TDLenalidomide treatmentEnhancing Personalized Prognostic Assessment of Myelodysplastic Syndromes through a Multimodal and Explainable Deep Data Fusion Approach (MAGAERA)
Sauta E, Sartori F, Lanino L, Asti G, D'Amico S, Delleani M, Riva E, Zampini M, Zazzetti E, Bicchieri M, Maggioni G, Campagna A, Todisco G, Tentori C, Ubezio M, Russo A, Buizza A, Ficara F, Crisafulli L, Brindisi M, Ventura D, Pinocchio N, Rahal D, Lancellotti C, Bonometti A, Di Tommaso L, Savevski V, Santoro A, Derus N, Dall'Olio D, Santini V, Sole F, Platzbecker U, Fenaux P, Diez-Campelo M, Komrokji R, Garcia-Manero G, Haferlach T, Kordasti S, Zeidan A, Castellani G, Sanavia T, Fariselli P, Della Porta M. Enhancing Personalized Prognostic Assessment of Myelodysplastic Syndromes through a Multimodal and Explainable Deep Data Fusion Approach (MAGAERA). Blood 2024, 144: 105-105. DOI: 10.1182/blood-2024-205413.Peer-Reviewed Original ResearchPersonalized medicine programsMyelodysplastic syndrome patientsMyelodysplastic syndromeOverall survivalConcordance indexClinical outcomesMay-Grunwald-GiemsaHypomethylating agentsBone marrowAnalysis of hematological malignanciesSomatic mutation screeningEvaluation of T lymphocytesResponse to hypomethylating agentsCD34+ bone marrowStudies of myelodysplastic syndromesGenomic featuresMDS populationRNA-seqPrediction of patient outcomeGenomic characterizationHarrell's concordance indexPredicting clinical outcomesHematoxylin and eosin (H&EMorphological dataMulti-omicsReal-World Use Patterns and Clinical Outcomes for Myelodysplastic Syndrome Patients Initiating Oral Decitabine and Cedazuridine or Intravenous/Subcutaneous Hypomethylating Agents
Zeidan A, Zhao R, Pierre-Victor D, Wang Y, Tepsick J, Lan Z, Salimi T. Real-World Use Patterns and Clinical Outcomes for Myelodysplastic Syndrome Patients Initiating Oral Decitabine and Cedazuridine or Intravenous/Subcutaneous Hypomethylating Agents. Blood 2024, 144: 5189-5189. DOI: 10.1182/blood-2024-205495.Peer-Reviewed Original ResearchAML-free survivalTreated with hypomethylating agentsOral hypomethylating agentsHypomethylating agentsMyelodysplastic syndrome patientsMyelodysplastic syndromeDEC-CClinical characteristicsMDS diagnosisNext treatmentMonths median follow-upRisk of AML transformationHigh-risk myelodysplastic syndromeReal-world treatment outcomesTreatment of adult patientsHypomethylating agent treatmentKaplan-Meier survival analysis methodMedian follow-upCox regression analysisReal-world studyAML transformationHMA therapyOral decitabineECOG 0Electronic health record databaseTargeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions
Bidikian A, Bewersdorf J, Shallis R, Getz T, Stempel J, Kewan T, Stahl M, Zeidan A. Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions. Expert Review Of Anticancer Therapy 2024, 24: 1131-1146. PMID: 39367718, DOI: 10.1080/14737140.2024.2414071.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsTargeted therapyLR-MDSHR-MDSHypoxia-inducible factorAllogeneic hematopoietic stem cell transplantationLandscape of targeted therapiesHematopoietic stem cell transplantationHeterogeneous group of hematologic malignanciesGroup of hematologic malignanciesMolecular prognostic toolsDuration of responseStem cell transplantationTrial designClinical trial designHypomethylating agentsCell transplantationHematologic malignanciesImprove patient outcomesRNA splicing machineryImmune evasionPrognostic toolTGF-betaTherapyEffective treatmentIntensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML
Bewersdorf J, Shimony S, Shallis R, Liu Y, Berton G, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Bystrom R, Lindsley R, Chen E, Perez J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML. Blood Advances 2024, 8: 4845-4855. PMID: 38941537, PMCID: PMC11416634, DOI: 10.1182/bloodadvances.2024012858.Peer-Reviewed Original ResearchIntensive induction chemotherapyAcute myeloid leukemiaNPM1-Mutant Acute Myeloid LeukemiaInduction chemotherapyHypomethylating agentsMulticenter retrospective cohort study of patientsPatients treated with ICAllogeneic stem cell transplantationRetrospective cohort study of patientsMulticenter retrospective cohort studyCohort study of patientsComposite complete remissionStem cell transplantationYears-oldFLT3-ITD mutationStudy of patientsStandard of careNormal cytogeneticsComplete remissionCell transplantationNPM1 mutationsMyeloid leukemiaFLT3-ITDYounger patientsOlder patientsMDS-772 Time Toxicity for Patients Receiving Oral Versus Parenteral Hypomethylating Agents for Myelodysplastic Syndromes/Neoplasms
Zeidan A, Olopoenia A, Costantino H, Modi K, Salimi T, Washington T, Krenitsky J, Epstein R. MDS-772 Time Toxicity for Patients Receiving Oral Versus Parenteral Hypomethylating Agents for Myelodysplastic Syndromes/Neoplasms. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s406. DOI: 10.1016/s2152-2650(24)01382-x.Peer-Reviewed Original ResearchHMA therapyRetrospective analysis of adult patientsAnalysis of adult patientsRoute of administrationMedian life expectancyPropensity score matchingHypomethylating agentsMDS treatmentBurden of treatmentAdult patientsPatient cohortInfusion dayParenteral treatmentMatched cohortResults PatientsRetrospective analysisOlder patientsEmergency room visitsCancer therapyHMA treatmentParenteral administrationTherapyPatientsOutpatient settingScore matchingTime Toxicity for Patients Receiving Oral Versus Parenteral Hypomethylating Agents for Myelodysplastic Syndromes/Neoplasms
Zeidan A, Olopoenia A, Costantino H, Modi K, Salimi T, Washington T, Krenitsky J, Epstein R. Time Toxicity for Patients Receiving Oral Versus Parenteral Hypomethylating Agents for Myelodysplastic Syndromes/Neoplasms. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s197. DOI: 10.1016/s2152-2650(24)00684-0.Peer-Reviewed Original ResearchHypomethylating agentsAcute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome
Alhajahjeh A, Bewersdorf J, Bystrom R, Zeidan A, Shimony S, Stahl M. Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome. Leukemia & Lymphoma 2024, 65: 1541-1551. PMID: 38962996, DOI: 10.1080/10428194.2024.2367040.Peer-Reviewed Original ResearchAcute myeloid leukemiaIntensive chemotherapyHypomethylating agentsMyeloid leukemiaAllogeneic stem cell transplantationAcute myeloid leukemia casesAcute myeloid leukemia subtypesStem cell transplantationComplex hematological malignancyCurrent treatment modalitiesRare genetic anomalyCell transplantationHematologic malignanciesTreatment modalitiesClinical outcomesTreatment responseInv(3Genetic alterationsLeukemia developmentTreatment strategiesCellular processesGenetic anomaliesLeukemiaFusion geneClinical implicationsTime toxicity for patients receiving oral versus parenteral hypomethylating agents for myelodysplastic syndromes/neoplasms (MDS).
Epstein R, Zeidan A, Olopoenia A, Costantino H, Modi K, Salimi T, Washington T, Krenitsky J. Time toxicity for patients receiving oral versus parenteral hypomethylating agents for myelodysplastic syndromes/neoplasms (MDS). Journal Of Clinical Oncology 2024, 42: 6568-6568. DOI: 10.1200/jco.2024.42.16_suppl.6568.Peer-Reviewed Original ResearchHMA therapyHypomethylating agentsRetrospective analysis of adult patientsAnalysis of adult patientsEmergency roomRoute of administrationTime burdenMedian life expectancyPropensity score matchingMDS treatmentBurden of treatmentAdult patientsParenteral treatmentPatient cohortInfusion dayRetrospective analysisCancer therapyPatientsTherapyOutpatient settingScore matchingTreatment groupsCohortHealthcare daysOutpatient visitsCombination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study
Bewersdorf J, Shimony S, Shallis R, Liu Y, Berton G, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Bystrom R, Lindsley R, Chen E, Ramos J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Combination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study. American Journal Of Hematology 2024, 99: 1640-1643. PMID: 38751104, DOI: 10.1002/ajh.27366.Peer-Reviewed Original ResearchTreatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 138-150. PMID: 38632155, DOI: 10.1007/s11899-024-00733-y.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationLower-risk MDSErythropoiesis-stimulating agentsHypomethylating agentsIPSS-MHR-MDSRisk stratificationMolecular International Prognostic Scoring SystemRisk of leukemia progressionTreated with hypomethylating agentsInternational Prognostic Scoring SystemTreatment of myelodysplastic syndromesOral hypomethylating agentsHigh-risk MDSPrognostic Scoring SystemStem cell transplantationEnhanced risk stratificationRecent FindingsRecent advancesRefine treatment strategiesQuality-of-life improvementAssociated with treatmentTreatment decision-makingIntensive chemotherapyMDS patientsClinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review
Haumschild R, Kennerly-Shah J, Barbarotta L, Zeidan A. Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review. Journal Of Oncology Pharmacy Practice 2024, 30: 721-736. PMID: 38509812, PMCID: PMC11118786, DOI: 10.1177/10781552241238979.Peer-Reviewed Original ResearchOral hypomethylating agentsAcute myeloid leukemiaHypomethylating agentsPK-PD profilesPharmacokinetic (PK)-pharmacodynamicMyeloid leukemiaTreatment selectionPK-PDConcentration-time curveIntravenous (IVImprove treatment outcomesCC-486IV decitabineOral azacitidineMaintenance therapySubcutaneous azacitidineNo significant differenceImprove quality of lifeAzacitidineClinical trialsClinical activityTreatment outcomesDisease settingsDecitabineDisease outcomeHypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML
Shimony S, Bewersdorf J, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos Perez J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML. Leukemia 2024, 38: 762-768. PMID: 38378841, DOI: 10.1038/s41375-024-02175-0.Peer-Reviewed Original ResearchAssociated with improved OSHypomethylating agentsCPX-351Overall survivalSplicing factor mutationsCo-mutationsAllogeneic hematopoietic stem cell transplantationAssociated with better OSAssociated with worse OSSecondary acute myeloid leukemiaHematopoietic stem cell transplantationMedian overall survivalStem cell transplantationPatients aged >Acute myeloid leukemiaTreated with daunorubicinLiposomal daunorubicinMonosomal karyotypeNRAS/KRAS mutationsImproved OSSecondary AMLMyeloid diseasesMyeloid neoplasmsAML patientsAML treatmentPatients’ perspectives on oral decitabine/cedazuridine for the treatment of myelodysplastic syndromes/neoplasms
Zeidan A, Perepezko K, Salimi T, Washington T, Epstein R. Patients’ perspectives on oral decitabine/cedazuridine for the treatment of myelodysplastic syndromes/neoplasms. Therapeutic Advances In Hematology 2024, 15: 20406207241257313. PMID: 39091323, PMCID: PMC11292726, DOI: 10.1177/20406207241257313.Peer-Reviewed Original ResearchHypomethylating agentsDEC-CQuality of lifeHypomethylating agent therapyGuideline-recommended treatmentHMA therapyOral therapySurvey of patientsTreatment side effectsAdult patientsImprove quality of lifeUS patientsSide effectsPatientsTreatment administrationTherapyDecitabine/cedazuridineTreatmentDaily activitiesMonthsLittle/no impact