2024
Prognostic impact of ‘multi-hit’ versus ‘single-hit’ TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases
Badar T, Nanaa A, Atallah E, Shallis R, Craver E, Li Z, Goldberg A, Saliba A, Patel A, Bewersdorf J, Duvall A, Burkart M, Bradshaw D, Abaza Y, Stahl M, Palmisiano N, Murthy S, Zeidan A, Kota V, Patnaik M, Litzow M. Prognostic impact of ‘multi-hit’ versus ‘single-hit’ TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases. Haematologica 2024, 109: 3533-3542. PMID: 38813716, PMCID: PMC11532685, DOI: 10.3324/haematol.2024.285000.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyelodysplastic syndromeComplex cytogeneticsMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationLower-risk myelodysplastic syndromesHematopoietic stem cell transplantationHigher-risk myelodysplastic syndromesOutcomes of SHStem cell transplantationAllo-HCTTP53 alterationsPrognostic impactMyeloid malignanciesTP53 mutationsCell transplantationFLT3-ITDIDH1 mutationMultivariate analysisSupportive careUS academic institutionsNeoplastic diseasePatientsSuperior EFSPredicting outcomeComparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Nanaa A, Atallah E, Shallis R, Guilherme S, Goldberg A, Saliba A, Patel A, Bewersdorf J, DuVall A, Bradshaw D, Abaza Y, Murthy G, Palmisiano N, Zeidan A, Kota V, Litzow M. Comparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood Cancer Journal 2024, 14: 32. PMID: 38378617, PMCID: PMC10879201, DOI: 10.1038/s41408-024-01000-2.Peer-Reviewed Original Research
2023
TP53 Y220C Mutations in Patients with Myeloid Malignancies
Gener-Ricos G, Bewersdorf J, Loghavi S, Goldberg A, Famulare C, Issa G, Borthakur G, Kadia T, Carter B, Patel K, Andreeff M, Stein E, DiNardo C. TP53 Y220C Mutations in Patients with Myeloid Malignancies. Blood 2023, 142: 1477. DOI: 10.1182/blood-2023-189343.Peer-Reviewed Original ResearchLeukemia-free survivalAcute myeloid leukemiaMedian leukemia-free survivalVariant allele frequencyMedian follow-upStem cell transplantationMyeloid neoplasmsHot spot mutationsTP53 mutationsCo-mutationsFollow-upMyelodysplastic syndromeMyeloid malignanciesOverall survivalHematologic malignanciesMyeloid leukemiaSolid tumorsTransformation to acute myeloid leukemiaMedian variant allele frequencyTherapy-related myeloid neoplasmsAcute myeloid leukemia transformationMemorial Sloan-Kettering Cancer CenterY220C mutationTP53 co-mutationsNext generation sequencing assayE7820, 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 trialE7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial
Bewersdorf J, Stahl M, Taylor J, Mi X, Chandhok N, Watts J, Derkach A, Wysocki M, Lu S, Bourcier J, Hogg S, Rahman J, Chaudhry S, Totiger T, Abdel-Wahab O, Stein E. E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial. Leukemia 2023, 37: 2512-2516. PMID: 37814121, PMCID: PMC10681888, DOI: 10.1038/s41375-023-02050-4.Peer-Reviewed Original ResearchConceptsPhase II clinical trialII clinical trialsMyeloid malignanciesClinical trialsMalignancyPatientsTargeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution
Santinelli E, Pascale M, Xie Z, Badar T, Stahl M, Bewersdorf J, Gurnari C, Zeidan A. Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution. Blood Reviews 2023, 62: 101130. PMID: 37679263, DOI: 10.1016/j.blre.2023.101130.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid malignanciesLeukemia cell survivalBcl-2 signalingPro-apoptotic agentsClinical studiesMyeloid leukemiaMyeloid neoplasmsTherapeutic revolutionMolecular alterationsMyeloid neoplasiaTherapeutic landscapeSpecific drugsApoptosis dysregulationSynergistic efficacyNew drugsMechanism of apoptosisDrugsMalignancyCombination strategiesCell survivalAttractive targetApoptotic pathwayTreatmentApoptosis
2022
Clinical Outcomes of Patients with TP53-Mutated AML after First Relapse or with Primary Refractory Disease: Results from Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Atallah E, Saliba A, Shallis R, Stahl M, Bewersdorf J, De Camargo Correia G, Patel A, Abaza Y, Murthy S, Duvall A, Burkart M, Palmisiano N, Bradshaw D, Kota V, Dinner S, Goldberg A, Litzow M. Clinical Outcomes of Patients with TP53-Mutated AML after First Relapse or with Primary Refractory Disease: Results from Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood 2022, 140: 6058-6060. DOI: 10.1182/blood-2022-163795.Peer-Reviewed Original ResearchPredictors of Long-Term Outcome in TP53-Mutated Acute Myeloid Leukemia Patients Receiving Allogeneic Stem Cell Transplant after First- or Second-Line Therapy: Results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Atallah E, Shallis R, Saliba A, Stahl M, Bewersdorf J, Grenet J, Patel A, Abaza Y, Murthy S, Duvall A, Burkart M, Palmisiano N, Kubiak M, Kota V, Dinner S, Goldberg A, Litzow M. Predictors of Long-Term Outcome in TP53-Mutated Acute Myeloid Leukemia Patients Receiving Allogeneic Stem Cell Transplant after First- or Second-Line Therapy: Results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood 2022, 140: 1435-1437. DOI: 10.1182/blood-2022-167731.Peer-Reviewed Original ResearchA Phase II Clinical Trial of E7820 for Patients with Relapsed/Refractory Myeloid Malignancies with Mutations in Splicing Factor Genes
Bewersdorf J, Stahl M, Taylor J, Chandhok N, Watts J, Derkach A, Wysocki M, Kostantakis V, Lu S, Bourcier J, Hogg S, Totiger T, Abdel-Wahab O, Stein E. A Phase II Clinical Trial of E7820 for Patients with Relapsed/Refractory Myeloid Malignancies with Mutations in Splicing Factor Genes. Blood 2022, 140: 9065-9067. DOI: 10.1182/blood-2022-156830.Peer-Reviewed Original Research
2021
Challenges in the Evaluation and Management of Toxicities Arising From Immune Checkpoint Inhibitor Therapy for Patients With Myeloid Malignancies
Shallis RM, Bewersdorf JP, Swoboda DM, Wei W, Gowda L, Prebet T, Halene S, Pillai MM, Parker T, Neparidze N, Podoltsev NA, Seropian S, Sallman DA, Gore SD, Zeidan AM. Challenges in the Evaluation and Management of Toxicities Arising From Immune Checkpoint Inhibitor Therapy for Patients With Myeloid Malignancies. Clinical Lymphoma Myeloma & Leukemia 2021, 21: e483-e487. PMID: 33551344, DOI: 10.1016/j.clml.2021.01.003.Peer-Reviewed Original Research
2020
Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways
Bewersdorf JP, Shallis RM, Zeidan AM. Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways. Blood Reviews 2020, 45: 100709. PMID: 32487480, DOI: 10.1016/j.blre.2020.100709.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsMyeloid malignanciesPD-1/PD-L1CTLA-4 pathwayImmune checkpoint inhibitionAcute myeloid leukemiaSafe combination therapyICI therapyImmunologic landscapeCheckpoint inhibitorsDisease coursePD-L1Checkpoint inhibitionMyelodysplastic syndromeCombination therapyMechanisms of resistanceClinical trialsMyeloid leukemiaClinical developmentPotential biomarkersNovel targetPatientsMalignancyTherapyBiomarkers