2023
E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial
Bewersdorf J, Chandhok N, Watts J, Derkach A, Abdel-Wahab O, Stein E, Taylor J. E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial. Blood 2023, 142: 1547. DOI: 10.1182/blood-2023-182369.Peer-Reviewed Original ResearchAcute myeloid leukemiaEastern Cooperative Oncology GroupPhase II clinical trialChronic myelomonocytic leukemiaMyelodysplastic syndromePatient-derived xenograftsII clinical trialsPreclinical dataSplicing factor genesMyeloid malignanciesClinical trialsAdequate end-organ functionContext of combination therapyDay 1Safety run-in phaseRefractory acute myeloid leukemiaSimon 2-stage designResponse rateDynamic BH3 profilingCycles of therapyNegative prognostic impactEvent-free survivalMyelodysplastic syndrome patientsHuman acute myeloid leukemiaPhase II trial
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 dataVenetoclaxInhibitorsGilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors
Numan Y, Rahman Z, Grenet J, Boisclair S, Bewersdorf JP, Collins C, Barth D, Fraga M, Bixby DL, Zeidan AM, Yilmaz M, Desai P, Mannis G, Deutsch YE, Abaza Y, Dinner S, Frankfurt O, Litzow M, Al‐Kali A, Foran JM, Sproat LZ, Jovanovic B, Daver N, Perl AE, Altman JK. Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors. American Journal Of Hematology 2022, 97: 322-328. PMID: 34981560, DOI: 10.1002/ajh.26447.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaRelapsed/Refractory Acute Myeloid LeukemiaComposite complete remission rateRefractory acute myeloid leukemiaLower median overall survivalComplete remission rateMedian overall survivalStem cell transplantCRC ratesLower CRCRefractory FLT3Median survivalRemission rateIntensive inductionOverall survivalCell transplantCombination therapyFLT3 inhibitorsFLT3 mutationsClinical activityUS CentersRetrospective analysisADMIRAL studyMitogen-activated protein kinase pathwayPhase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes
Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 557-569. PMID: 34981142, PMCID: PMC9414073, DOI: 10.1007/s00277-021-04734-2.Peer-Reviewed Original ResearchConceptsAnti-drug antibodiesAcute myeloid leukemiaDose-limiting toxicityRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeMyelodysplastic syndromeMyeloid leukemiaCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsADA-positive patientsPhase 2 dosePresence/frequencyUnexpected safety findingsPhase 1 studyAnti-CD47 antibodyCD47-SIRPα interactionMacrophage-mediated killingHematological cancer cell linesFebrile neutropeniaMonotherapy activityCancer cell linesPrimary endpointSecondary endpointsAdverse eventsObjective response
2020
Venetoclax as monotherapy and in combination with hypomethylating agents or low dose cytarabine in relapsed and treatment refractory acute myeloid leukemia: a systematic review and meta-analysis
Bewersdorf JP, Giri S, Wang R, Williams RT, Tallman MS, Zeidan AM, Stahl M. Venetoclax as monotherapy and in combination with hypomethylating agents or low dose cytarabine in relapsed and treatment refractory acute myeloid leukemia: a systematic review and meta-analysis. Haematologica 2020, 105: 2659-2663. PMID: 33131256, PMCID: PMC7604631, DOI: 10.3324/haematol.2019.242826.Peer-Reviewed Original ResearchConceptsRefractory acute myeloid leukemiaLow-dose cytarabineAcute myeloid leukemiaDose cytarabineMyeloid leukemiaSystematic reviewMonotherapyCytarabineVenetoclaxLeukemia