{"doi":"10.1002/ajh.26281","title":"Impact of <scp>Philadelphia</scp> chromosome‐like alterations on efficacy and safety of blinatumomab in adults with relapsed/refractory acute lymphoblastic leukemia: A post hoc analysis from the phase 3 <scp>TOWER</scp> study","abstract":"Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subgroup of precursor B-cell (BCP) ALL. Patients with Ph-like ALL have a gene expression profile (GEP) similar to those with Ph+ ALL, but lack the characteristic BCR-ABL1 fusion. Among these patients, inferior outcomes are observed compared with those without Ph-like ALL.1 A standard treatment approach does not yet exist for the treatment of patients with Ph-like ALL. Blinatumomab, a BiTE® (bispecific T-cell engager) molecule, is effective in adults and children with relapsed/refractory (R/R) BCP ALL and persistent minimal residual disease (MRD).2 Results from a randomized, multicenter, phase 3 trial in adult patients with R/R BCP ALL (TOWER; NCT02013167) demonstrated significantly longer median overall survival (OS) with blinatumomab compared with standard of care chemotherapy (SOC; 7.7 months vs. 4.0 months, p = 0.01).3 Here, we report the results of a post hoc analysis of the TOWER trial that evaluated the impact of the Ph-like alterations on the efficacy and safety of blinatumomab and SOC in patients with R/R BCP ALL. The previously reported TOWER study conducted in adult patients with R/R BCP ALL compared the efficacy and safety of blinatumomab with SOC3. Of the 405 patients randomly assigned in a 2:1 ratio to receive blinatumomab (n = 271) or SOC (n = 134), stored and available samples from 142 patients were analyzed at the MD Anderson Cancer Center (MDACC; MDACC analysis set) in this post hoc study. A comprehensive targeted next-generation sequencing assay, which identifies fusions, point mutations, expression levels in 81 genes associated with ALL, and all recurrent Ph-like ALL fusion events, was performed on RNA extracted from samples of these patients (n = 142) using a multiplex fusion and mutation detection assay (Archer® FusionPlex® ALL, ArcherDX, Inc., Colorado, USA; Table S1). Details of targeted Ph-like ALL testing and RNA sequencing are described in the supplement. Efficacy analyses and baseline characteristics were performed on the MDACC analysis set and safety analyses were performed on patients included in the MDACC analysis set, who received at least one dose of blinatumomab or SOC. Descriptive analysis was used to summarize demographics and safety data. The proportion of patients who achieved responses, including complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete hematologic recovery (CRi), and MRD remission, was summarized with exact 95% confidence intervals (CIs). The Kaplan–Meier method was used to estimate OS. The hazard ratio (HR) estimates were obtained from the Cox proportional hazard model with stratification factors of age (<35 vs. ≥35 years), prior salvage therapy (yes vs. no), and prior allogeneic hematopoietic stem cell transplantation (alloHSCT; yes vs no). Of the 142 samples analyzed for the Ph-like ALL alterations, 101 (71%) were from patients treated with blinatumomab and 41 (29%) from patients with SOC (Table S2). As analyzed by RNA sequencing, a total of 15 (11%) patients had Ph-like ALL; nine were treated with blinatumomab and six with SOC. Demographics and baseline characteristics of patients in this post hoc study were similar to those of patients enrolled in the phase 3 TOWER study.3 Among the 15 patients identified with Ph-like ALL, RCSD1-ABL1, SQSTM1-JAK2, ZMYM2-FGFR1, ATF7IP-JAK2, ETV6-ABL1, JAK2-CCDC171, PAX5-JAK2, and IGH-CRLF2 were observed in one (7%) patient each, EPOR-IGH and EBF1-PDGFRB were observed in two (13%) patients each, and P2RY8-CRLF2 was observed in three (20%) patients. Remission rates within 12 weeks of treatment initiation with blinatumomab were similar in patients with (n = 9) and without (n = 92) Ph-like ALL with respect to CR (33% vs. 36%, respectively) and CRh (11% vs. 10%, respectively; Table S3). Among patients receiving blinatumomab who had CR, CRh, or CRi, two of four (50%) patients with Ph-like ALL and 18 of 43 (42%) patients without ","journal":"American Journal of Hematology","year":2021,"id":167381,"datarank":0.9523906236406887,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.42791448942071664,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.42791448942071664,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":22,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02013167"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":33069,"name":"Keyur P. Patel","orcid":"0000-0001-5081-2427","position":1,"is_corresponding":false},{"id":232850,"name":"Nitin Jain","orcid":"0000-0003-0114-8384","position":2,"is_corresponding":false},{"id":311143,"name":"Dzifa Y. Duose","orcid":"0000-0002-6763-9736","position":3,"is_corresponding":false},{"id":397800,"name":"Rajyalakshmi Luthra","orcid":"0000-0002-7133-0221","position":4,"is_corresponding":false},{"id":230993,"name":"Nicholas J. Short","orcid":"0000-0002-2983-2738","position":5,"is_corresponding":false},{"id":484634,"name":"Gerhard Zugmaier","orcid":"0000-0001-6879-2671","position":6,"is_corresponding":false},{"id":695726,"name":"Anthony San Lucas","orcid":null,"position":7,"is_corresponding":false},{"id":694746,"name":"Kelly Velasco","orcid":"0000-0002-9376-6034","position":8,"is_corresponding":false},{"id":520377,"name":"Qui Tran","orcid":"0000-0002-0760-964X","position":9,"is_corresponding":false},{"id":694747,"name":"Faraz Zaman","orcid":"0000-0002-0758-4630","position":10,"is_corresponding":false},{"id":18373,"name":"Marina Konopleva","orcid":"0000-0002-9347-2212","position":11,"is_corresponding":false},{"id":109598,"name":"Hagop M. Kantarjian","orcid":"0000-0002-1908-3307","position":12,"is_corresponding":false},{"id":230404,"name":"Elias Jabbour","orcid":"0000-0003-4465-6119","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-18T23:45:58.359801Z","pmid":"34161631","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":[]}