{"doi":"10.1002/ajh.70048","title":"Contemporary Outcomes of Adults With Acute Lymphoblastic Leukemia With <scp> <i>KMT2A</i> </scp> Rearrangements Treated With Immunotherapy‐Based Regimens","abstract":"Formerly known as mixed-lineage leukemia gene, KMT2A portends a poor outcome when rearranged in patients with B-cell acute lymphoblastic leukemia (ALL) [1]. Despite advancements in the treatment of Philadelphia (Ph)-negative ALL, adults with KMT2A-rearrangements have a median overall survival (mOS) of 14 months, with a 5-year OS of 15% [2]. There is an unmet need to identify efficacious agents to reduce relapses and improve long-term survival for this high-risk group. The incorporation of the monoclonal antibody blinatumomab into frontline treatment for Ph-negative ALL has been transformative. While infants with KMT2A-rearranged ALL demonstrate improved outcomes when treated with frontline blinatumomab with chemotherapy compared to chemotherapy alone, data in adults with KMT2A-rearranged ALL are limited [3]. Herein, we assess the impact of immunotherapy-based regimens compared to a historical cohort of patients treated with HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) in KMT2A-rearranged B-ALL. We performed a retrospective analysis of patients ≥ 18 years old with newly diagnosed (ND) B-ALL treated between January 2000 and October 2024 to identify patients with KMT2A rearrangements (KMT2Ar). KMT2Ar were identified via conventional cytogenetics and/or fluorescence in situ hybridization (FISH). We compared the outcomes of patients treated with the addition of inotuzumab-ozogamicin and/or blinatumomab to HyperCVAD (HCVAD-InO/Blina cohort) to our historical cohort of patients treated with HyperCVAD alone (HCVAD cohort). This study was approved by the MD Anderson Cancer Center Institutional Review Board and conducted in compliance with the Declaration of Helsinki. We assessed the composite complete remission (CRc) rate (defined as CR or CR with incomplete count recovery [CRi]); OS and event-free survival (EFS) were evaluated by the Kaplan–Meier method, with subgroup comparisons by log-rank testing. The cumulative incidence of relapse (CIR) was calculated with Gray's test using relapse as the primary event and death without relapse as a competing event. Measurable residual disease (MRD) was evaluated with multiparameter flow cytometry (MFC, sensitivity 10−4) and via next-generation sequencing (NGS, sensitivity 10−6; clonoSEQ; Adaptive Biotechnologies Co., Seattle, WA). A landmark analysis assessed the impact of allogeneic stem cell transplantation (allo-SCT) in first CR (CR1). Multivariable analysis (MVA) was performed using Cox regression to assess outcomes between treatment cohorts and survival, adjusting for relevant covariates. Data analysis was performed with R-4.4.0. Table 1 summarizes the baseline characteristics and responses of the included patients. Out of patients ≥ 18 years old with ND Ph-negative B-ALL, 53/1190 (5%) had KMT2Ar, with an incidence of 6% (26/450) in the HCVAD-InO/Blina cohort versus 4% (27/740) in the HCVAD cohort. Of the 53 patients with KMT2Ar, 26 patients (49%) were treated with HyperCVAD (HCVAD cohort), and 22 patients (42%) were treated with chemotherapy ± InO ± Blina (HCVAD-InO/Blina cohort), generating our total study population of 48 patients. Fifty-two percent of patients in the HCVAD-InO/Blina cohort received the Hyper-CVAD backbone, with most of the remaining patients (27%) receiving mini-CVD chemotherapy. Sixty percent of patients in the HCVAD-InO/Blina cohort received blinatumomab and inotuzumab, 32% received blinatumomab alone, and 8% received inotuzumab alone. The median age at diagnosis in the HCVAD-InO/Blina cohort was 55 years (range, 19–83) versus 48 years (25–75) in the HCVAD cohort (p = 0.372). The most common cytogenetic abnormality, t(4;11), was identified in 41% in the HCVAD-InO/Blina cohort versus 88% of the HCVAD cohort (p = 0.001), although the different time periods and available testing likely explain these differences. The median baseline white blood cell (WBC) count was 32 × 1","journal":"American Journal of Hematology","year":2025,"id":573467,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230404,"name":"Elias Jabbour","orcid":"0000-0003-4465-6119","position":1,"is_corresponding":false},{"id":230993,"name":"Nicholas J. Short","orcid":"0000-0002-2983-2738","position":2,"is_corresponding":false},{"id":232850,"name":"Nitin Jain","orcid":"0000-0003-0114-8384","position":3,"is_corresponding":false},{"id":232845,"name":"Ghayas C. Issa","orcid":"0000-0002-4339-8683","position":4,"is_corresponding":false},{"id":883433,"name":"Himachandana Atluri","orcid":"0000-0002-8867-7774","position":5,"is_corresponding":false},{"id":1032154,"name":"Álex Bataller","orcid":"0000-0002-6085-2745","position":6,"is_corresponding":false},{"id":232841,"name":"Tapan M. Kadia","orcid":"0000-0002-9892-9832","position":7,"is_corresponding":false},{"id":232840,"name":"Naval Daver","orcid":"0000-0001-7103-373X","position":8,"is_corresponding":false},{"id":109577,"name":"Courtney D. DiNardo","orcid":"0000-0001-9003-0390","position":9,"is_corresponding":false},{"id":1050005,"name":"Rebecca Garris","orcid":"0000-0001-8009-5529","position":10,"is_corresponding":false},{"id":1060773,"name":"Jayastu Senapati","orcid":"0000-0002-6831-2567","position":11,"is_corresponding":false},{"id":230403,"name":"Farhad Ravandi","orcid":"0000-0002-7621-377X","position":12,"is_corresponding":false},{"id":109598,"name":"Hagop M. Kantarjian","orcid":"0000-0002-1908-3307","position":13,"is_corresponding":false},{"id":1242534,"name":"Hannah Goulart","orcid":"0000-0002-1945-2571","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-19T02:57:32.445190Z","pmid":"40862325","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":[]}