{"doi":"10.1182/blood.2020007732","title":"Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia","abstract":"Approximately 50% of acute myeloid leukemia (AML) patients do not respond to induction therapy (primary induction failure [PIF]) or relapse after <6 months (early relapse [ER]). We have recently shown an association between an immune-infiltrated tumor microenvironment (TME) and resistance to cytarabine-based chemotherapy but responsiveness to flotetuzumab, a bispecific DART antibody-based molecule to CD3ε and CD123. This paper reports the results of a multicenter, open-label, phase 1/2 study of flotetuzumab in 88 adults with relapsed/refractory AML: 42 in a dose-finding segment and 46 at the recommended phase 2 dose (RP2D) of 500 ng/kg per day. The most frequent adverse events were infusion-related reactions (IRRs)/cytokine release syndrome (CRS), largely grade 1-2. Stepwise dosing during week 1, pretreatment dexamethasone, prompt use of tocilizumab, and temporary dose reductions/interruptions successfully prevented severe IRR/CRS. Clinical benefit accrued to PIF/ER patients showing an immune-infiltrated TME. Among 30 PIF/ER patients treated at the RP2D, the complete remission (CR)/CR with partial hematological recovery (CRh) rate was 26.7%, with an overall response rate (CR/CRh/CR with incomplete hematological recovery) of 30.0%. In PIF/ER patients who achieved CR/CRh, median overall survival was 10.2 months (range, 1.87-27.27), with 6- and 12-month survival rates of 75% (95% confidence interval [CI], 0.450-1.05) and 50% (95% CI, 0.154-0.846). Bone marrow transcriptomic analysis showed that a parsimonious 10-gene signature predicted CRs to flotetuzumab (area under the receiver operating characteristic curve = 0.904 vs 0.672 for the European LeukemiaNet classifier). Flotetuzumab represents an innovative experimental approach associated with acceptable safety and encouraging evidence of activity in PIF/ER patients. This trial was registered at www.clinicaltrials.gov as #NCT02152956.","journal":"Blood","year":2020,"id":48912,"datarank":4.033864115991316,"base_score":5.777652323222656,"endowment":5.777652323222656,"self_citation_contribution":0.8666478484833986,"citation_network_contribution":3.1672162675079165,"self_endowment_contribution":0.8666478484833986,"citer_contribution":3.1672162675079165,"corpus_percentile":null,"corpus_rank":null,"citation_count":322,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02152956"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":233349,"name":"Ibrahim Aldoss","orcid":"0000-0001-9564-4498","position":1,"is_corresponding":false},{"id":233350,"name":"Matthew C. Foster","orcid":"0000-0002-6652-3838","position":2,"is_corresponding":false},{"id":234616,"name":"Peter H. Sayre","orcid":null,"position":3,"is_corresponding":false},{"id":233351,"name":"Matthew J. Wieduwilt","orcid":"0000-0002-5414-9228","position":4,"is_corresponding":false},{"id":233352,"name":"Anjali S. Advani","orcid":"0000-0003-0015-5902","position":5,"is_corresponding":false},{"id":233353,"name":"John E. Godwin","orcid":"0000-0003-3876-2505","position":6,"is_corresponding":false},{"id":233354,"name":"Martha Arellano","orcid":"0000-0003-1636-1962","position":7,"is_corresponding":false},{"id":233355,"name":"Kendra Sweet","orcid":"0000-0001-6248-3317","position":8,"is_corresponding":false},{"id":233356,"name":"Ashkan Emadi","orcid":"0000-0003-3769-3210","position":9,"is_corresponding":false},{"id":230403,"name":"Farhad Ravandi","orcid":"0000-0002-7621-377X","position":10,"is_corresponding":false},{"id":233357,"name":"Harry P. Erba","orcid":"0000-0003-1093-2189","position":11,"is_corresponding":false},{"id":233358,"name":"Michael Byrne","orcid":"0000-0002-2966-4877","position":12,"is_corresponding":false},{"id":233359,"name":"Laura C. Michaelis","orcid":"0000-0002-1798-9658","position":13,"is_corresponding":false},{"id":233360,"name":"Max S. Topp","orcid":"0000-0002-1267-5289","position":14,"is_corresponding":false},{"id":233361,"name":"Norbert Vey","orcid":"0000-0001-7027-040X","position":15,"is_corresponding":false},{"id":104174,"name":"Fabio Ciceri","orcid":"0000-0003-0873-0123","position":16,"is_corresponding":false},{"id":233362,"name":"Matteo Giovanni Carrabba","orcid":"0000-0001-7015-4839","position":17,"is_corresponding":false},{"id":233363,"name":"Stefania Paolini","orcid":"0000-0002-5645-0364","position":18,"is_corresponding":false},{"id":233364,"name":"Gerwin Huls","orcid":"0009-0001-6789-6433","position":19,"is_corresponding":false},{"id":234617,"name":"Mojca Jongen‐Lavrencic","orcid":null,"position":20,"is_corresponding":false},{"id":233365,"name":"Martin Wermke","orcid":"0000-0002-4844-4087","position":21,"is_corresponding":false},{"id":233366,"name":"Patrice Chevallier","orcid":"0000-0003-3142-5581","position":22,"is_corresponding":false},{"id":233367,"name":"Emmanuel Gyan","orcid":"0000-0002-7651-9189","position":23,"is_corresponding":false},{"id":233368,"name":"Christian Récher","orcid":"0000-0002-3332-4525","position":24,"is_corresponding":false},{"id":11107,"name":"Patrick J. Stiff","orcid":"0000-0001-8265-9340","position":25,"is_corresponding":false},{"id":233369,"name":"Kristen Pettit","orcid":"0009-0007-3536-4137","position":26,"is_corresponding":false},{"id":233370,"name":"Bob Löwenberg","orcid":"0000-0001-8982-5217","position":27,"is_corresponding":false},{"id":87447,"name":"S. Church","orcid":"0000-0002-7194-4282","position":28,"is_corresponding":false},{"id":234618,"name":"Erica Anderson","orcid":null,"position":29,"is_corresponding":false},{"id":233371,"name":"Jayakumar Vadakekolathu","orcid":"0000-0002-2671-4285","position":30,"is_corresponding":false},{"id":234619,"name":"Marianne Santaguida","orcid":null,"position":31,"is_corresponding":false},{"id":233372,"name":"Michael P. Rettig","orcid":"0000-0002-1091-0564","position":32,"is_corresponding":false},{"id":234620,"name":"John Muth","orcid":null,"position":33,"is_corresponding":false},{"id":234621,"name":"Teia Curtis","orcid":null,"position":34,"is_corresponding":false},{"id":234622,"name":"Erin Fehr","orcid":null,"position":35,"is_corresponding":false},{"id":233373,"name":"Kuo Guo","orcid":"0009-0006-9360-5464","position":36,"is_corresponding":false},{"id":140971,"name":"Jian Zhao","orcid":"0000-0001-8015-3151","position":37,"is_corresponding":false},{"id":234623,"name":"Ouiam Bakkacha","orcid":null,"position":38,"is_corresponding":false},{"id":233374,"name":"Kenneth Jacobs","orcid":"0000-0002-7544-9772","position":39,"is_corresponding":false},{"id":233375,"name":"Kathy Tran","orcid":"0009-0001-3515-3432","position":40,"is_corresponding":false},{"id":234624,"name":"Patrick Kaminker","orcid":null,"position":41,"is_corresponding":false},{"id":234625,"name":"Maya Kostova","orcid":null,"position":42,"is_corresponding":false},{"id":233376,"name":"Ezio Bonvini","orcid":"0000-0001-9054-3137","position":43,"is_corresponding":false},{"id":230996,"name":"Roland B. Walter","orcid":"0000-0002-9268-3341","position":44,"is_corresponding":false},{"id":233377,"name":"Jan Davidson‐Moncada","orcid":"0000-0001-5550-8088","position":45,"is_corresponding":false},{"id":233378,"name":"Sergio Rutella","orcid":"0000-0003-1970-7375","position":46,"is_corresponding":false},{"id":18437,"name":"John F. Dipersio","orcid":"0000-0002-0429-3133","position":47,"is_corresponding":false},{"id":233348,"name":"Geoffrey L. Uy","orcid":"0000-0002-7809-0996","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T20:35:18.908826Z","pmid":"32929488","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}