{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T21:34:29Z","timestamp":1765056869407,"version":"3.46.0"},"reference-count":51,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>With the addition of antibody-based immunotherapy to frontline treatment regimens for B-lineage acute lymphoblastic leukemia (B-ALL), patients across the age spectrum now experience superior long-term survival. The pressing question for the field is whether immunotherapy may replace some of the intensive elements of the standard chemotherapy backbone to reduce overall toxicity and duration while maintaining superior outcomes. For young adults with B-ALL, most clinical trials have added immunotherapy to the intensive, pediatric-inspired regimens to achieve deeper remissions, while necessarily increasing duration, complexity, and possible toxicities. In contrast, clinical trials for older adults have used immunotherapy as a substitute to eliminate or reduce cytotoxic chemotherapy. And although survival outcomes for older adults remain distinctly inferior to those in the pediatric age group, it is hoped that the potential simplification of the chemoimmunotherapy backbone for all patients may be guided by the successes and shortcomings discovered in the treatment of older adults. In this article, I discuss the treatment of older adult patients with B-ALL in the immunotherapy era and how this approach may pave the way for implementing a deescalation strategy for younger adult patients with B-ALL, while maintaining the significant survival benefits that have been achieved during the past 20 years.<\/jats:p>","DOI":"10.1182\/hematology.2025000710","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:08:10Z","timestamp":1764943690000},"page":"236-244","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Immune targeting in Ph-negative and Ph-positive B-ALL: improving outcomes and minimizing chemotherapy in adult B-ALL"],"prefix":"10.1182","volume":"2025","author":[{"given":"Kristen M.","family":"O'Dwyer","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, University of Rochester School of Medicine, Rochester, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"2025120616325442100_hem2025000710C1","unstructured":"ONS Voice. FDA approves blinatumomab as consolidation for CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. 14June, 2024. https:\/\/www.ons.org\/publications-research\/voice\/news-views\/06-2024\/fda-approves-blinatumomab-consolidation-cd19."},{"issue":"4","key":"2025120616325442100_hem2025000710C2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa2312948","article-title":"Blinatumomab for MRD-negative acute lymphoblastic leukemia in adults","volume":"391","author":"Litzow","year":"2024","journal-title":"N Engl J Med"},{"issue":"9","key":"2025120616325442100_hem2025000710C3","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1056\/NEJMoa2411680","article-title":"Blinatumomab in standard-risk B-cell acute lymphoblastic leukemia in children","volume":"392","author":"Gupta","year":"2025","journal-title":"N Engl J Med"},{"issue":"3","key":"2025120616325442100_hem2025000710C4","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1182\/blood-2008-04-149286","article-title":"Patients' age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group","volume":"112","author":"Burmeister","year":"2008","journal-title":"Blood"},{"issue":"11","key":"2025120616325442100_hem2025000710C5","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.3324\/haematol.2012.080432","article-title":"Clinico-biologic characterization of 5203 acute lymphoblastic leukemia patients enrolled in the Italian AIEOP and GIMEMA protocols, stratified in age-cohorts","volume":"98","author":"Chiaretti","year":"2013","journal-title":"Haematologica"},{"issue":"19","key":"2025120616325442100_hem2025000710C6","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1056\/NEJMra2405573","article-title":"Ph-positive acute lymphoblastic leukemia\u201425 years of progress","volume":"392","author":"Fo\u00e0","year":"2025","journal-title":"N Engl J Med"},{"issue":"14","key":"2025120616325442100_hem2025000710C7","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJM200104053441402","article-title":"Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome","volume":"344","author":"Druker","year":"2001","journal-title":"N Engl J Med"},{"issue":"6","key":"2025120616325442100_hem2025000710C8","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1182\/blood-2001-12-0181","article-title":"A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome\u2013positive acute lymphoid leukemias","volume":"100","author":"Ottmann","year":"2002","journal-title":"Blood"},{"issue":"7","key":"2025120616325442100_hem2025000710C9","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1182\/blood-2002-03-0704","article-title":"Outcome of treatment in adults with Philadelphia chromosome\u2013positive acute lymphoblastic leukemia\u2014-results of the prospective multicenter LALA-94 trial","volume":"100","author":"Dombret","year":"2002","journal-title":"Blood"},{"issue":"9","key":"2025120616325442100_hem2025000710C10","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1182\/blood-2004-07-2922","article-title":"A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol","volume":"105","author":"Mancini","year":"2005","journal-title":"Blood"},{"issue":"19","key":"2025120616325442100_hem2025000710C11","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1182\/blood-2009-01-199380","article-title":"Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII\/ECOG2993","volume":"113","author":"Fielding","year":"2009","journal-title":"Blood"},{"issue":"6","key":"2025120616325442100_hem2025000710C12","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1182\/blood-2013-09-529008","article-title":"UKALLXII\/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia","volume":"123","author":"Fielding","year":"2014","journal-title":"Blood"},{"issue":"23","key":"2025120616325442100_hem2025000710C13","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1002\/cncr.29646","article-title":"Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia","volume":"121","author":"Ravandi","year":"2015","journal-title":"Cancer"},{"issue":"3","key":"2025120616325442100_hem2025000710C14","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/ajh.26816","article-title":"Frontline combination of ponatinib and hyper-CVAD in Philadelphia chromosome-positive acute lymphoblastic leukemia: 80-months follow-up results","volume":"98","author":"Kantarjian","year":"2023","journal-title":"Am J Hematol"},{"issue":"5","key":"2025120616325442100_hem2025000710C15","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1182\/blood-2005-11-4386","article-title":"Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)","volume":"108","author":"Wassmann","year":"2006","journal-title":"Blood"},{"issue":"4","key":"2025120616325442100_hem2025000710C16","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1182\/blood-2006-03-011908","article-title":"Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome\u2013positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study","volume":"109","author":"de Labarthe","year":"2007","journal-title":"Blood"},{"issue":"6","key":"2025120616325442100_hem2025000710C17","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1182\/blood-2016-02-700153","article-title":"Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome\u2013positive ALL","volume":"128","author":"Rousselot","year":"2016","journal-title":"Blood"},{"issue":"9","key":"2025120616325442100_hem2025000710C18","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1182\/blood-2006-10-052746","article-title":"Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol","volume":"109","author":"Vignetti","year":"2007","journal-title":"Blood"},{"issue":"9","key":"2025120616325442100_hem2025000710C19","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1038\/sj.leu.2404320","article-title":"Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study","volume":"20","author":"Delannoy","year":"2006","journal-title":"Leukemia"},{"issue":"25","key":"2025120616325442100_hem2025000710C20","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.1182\/blood-2011-05-351403","article-title":"Dasatinib as first-line treatment for adult patients with Philadelphia chromosome\u2013positive acute lymphoblastic leukemia","volume":"118","author":"Fo\u00e0","year":"2011","journal-title":"Blood"},{"issue":"12","key":"2025120616325442100_hem2025000710C21","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.3324\/haematol.2016.144535","article-title":"A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study","volume":"101","author":"Chiaretti","year":"2016","journal-title":"Haematologica"},{"issue":"17","key":"2025120616325442100_hem2025000710C22","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1056\/NEJMoa2016272","article-title":"Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults","volume":"383","author":"Fo\u00e0","year":"2020","journal-title":"N Engl J Med"},{"issue":"7","key":"2025120616325442100_hem2025000710C23","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1182\/bloodadvances.2022008216","article-title":"Dasatinib\/prednisone induction followed by blinatumomab\/dasatinib in Ph+ acute lymphoblastic leukemia","volume":"7","author":"Advani","year":"2023","journal-title":"Blood Adv"},{"issue":"1","key":"2025120616325442100_hem2025000710C24","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1016\/S2352-3026(22)00319-2","article-title":"Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial","volume":"10","author":"Jabbour","year":"2023","journal-title":"Lancet Haematol"},{"issue":"36","key":"2025120616325442100_hem2025000710C25","doi-asserted-by":"publisher","first-page":"4246","DOI":"10.1200\/JCO.24.00272","article-title":"Results of the simultaneous combination of ponatinib and blinatumomab in Philadelphia chromosome- positive ALL","volume":"42","author":"Kantarjian","year":"2024","journal-title":"J Clin Oncol"},{"key":"2025120616325442100_hem2025000710C26","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1182\/blood-2024-207892","article-title":"Efficacy and toxicity of frontline Ponatinib plus blinatumomab for adult Ph+ ALL patients of all ages: intermediate analysis of the Gimema ALL2820","volume":"144","author":"Chiaretti","year":"2024","journal-title":"Blood"},{"issue":"7","key":"2025120616325442100_hem2025000710C27","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1002\/cncr.28522","article-title":"Drug resistance and BCR-ABL kinase domain mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia from the imatinib to the second-generation tyrosine kinase inhibitor era: the main changes are in the type of mutations, but not in the frequency of mutation involvement","volume":"120","author":"Soverini","year":"2014","journal-title":"Cancer"},{"issue":"1","key":"2025120616325442100_hem2025000710C28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13045-025-01709-y","article-title":"Molecular characterization and predictors of relapse in patients with Ph + ALL after frontline ponatinib and blinatumomab","volume":"18","author":"Short","year":"2025","journal-title":"J Hematol Oncol"},{"issue":"8","key":"2025120616325442100_hem2025000710C29","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1200\/JCO.23.01075","article-title":"Long-term results of the dasatinib-blinatumomab protocol for adult Philadelphia-positive ALL","volume":"42","author":"Fo\u00e0","year":"2024","journal-title":"J Clin Oncol"},{"issue":"7","key":"2025120616325442100_hem2025000710C30","doi-asserted-by":"crossref","first-page":"e510","DOI":"10.1016\/S2352-3026(23)00088-1","article-title":"Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372\/COG AALL1122): a single-arm, multicentre, phase 2 trial","volume":"10","author":"Hunger","year":"2023","journal-title":"Lancet Haematol"},{"key":"2025120616325442100_hem2025000710C31","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1182\/blood-2024-208824","article-title":"Low intensity mini-hypercvd (mHCVD), inotuzumab ozogamicin (Ino) with\/without blinatumomab (Blina) in older patients with newly diagnosed Philadelphia negative B-cell acute lymphoblastic leukemia (B-ALL): 10 years update","volume":"144","author":"Senapati","year":"2024","journal-title":"Blood"},{"issue":"3","key":"2025120616325442100_hem2025000710C32","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1200\/JCO.23.00546","article-title":"Inotuzumab ozogamicin as induction therapy for patients older than 55 years with Philadelphia chromosome-negative B-precursor ALL","volume":"42","author":"Stelljes","year":"2024","journal-title":"J Clin Oncol"},{"issue":"36","key":"2025120616325442100_hem2025000710C33","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.1200\/JCO.24.00490","article-title":"Inotuzumab ozogamicin and low-intensity chemotherapy in older patients with newly diagnosed CD22+ Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia","volume":"42","author":"Chevallier","year":"2024","journal-title":"J Clin Oncol"},{"issue":"14","key":"2025120616325442100_hem2025000710C34","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1200\/JCO.21.01766","article-title":"SWOG 1318: a Phase II trial of blinatumomab followed by POMP maintenance in older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia","volume":"40","author":"Advani","year":"2022","journal-title":"J Clin Oncol"},{"issue":"suppl 1","key":"2025120616325442100_hem2025000710C35","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1182\/blood-2023-180472","article-title":"Dose reduced chemotherapy in sequence with blinatumomab for newly diagnosed older patients with Ph\/BCR::ABL negative B-precursor adult lymphoblastic leukemia (ALL): preliminary results of the GMALL bold trial","volume":"142","author":"Goekbuget","year":"2023","journal-title":"Blood"},{"issue":"2","key":"2025120616325442100_hem2025000710C36","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S1470-2045(18)30011-1","article-title":"Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study","volume":"19","author":"Kantarjian","year":"2018","journal-title":"Lancet Oncol"},{"key":"2025120616325442100_hem2025000710C37","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1182\/blood-2024-208742","article-title":"Chemotherapy free regimen of inotuzumab ozogamicin and blinatumomab in frontline therapy of older patients with Philadelphia negative B-cell acute lymphoblastic leukemia","volume":"144","author":"Senapati","year":"2024","journal-title":"Blood"},{"issue":"suppl 3","key":"2025120616325442100_hem2025000710C38","article-title":"Chemotherapy-free treatment with inotuzumab ozogamicin and blinatumomab for older adults with newly diagnosed, Ph-negative, CD22-positive, B-cell acute lymphoblastic leukemia: alliance A041703","volume":"7","author":"Wieduwilt","year":"2023","journal-title":"HemaSphere"},{"issue":"3","key":"2025120616325442100_hem2025000710C39","doi-asserted-by":"crossref","first-page":"e473298","DOI":"10.1200\/EDBK-25-473298","article-title":"Treatment of older patients with ALL","volume":"45","author":"Jabbour","year":"2025","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"2025120616325442100_hem2025000710C40","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1182\/blood-2024-201784","article-title":"CD19-CAR T cells as definitive consolidation for older adults with B-cell acute lymphoblastic leukemia in first complete remission: a pilot study","volume":"144","author":"Aldoss","year":"2024","journal-title":"Blood"},{"issue":"20","key":"2025120616325442100_hem2025000710C41","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1200\/JCO.2015.62.4544","article-title":"Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group study AALL0232","volume":"34","author":"Larsen","year":"2016","journal-title":"J Clin Oncol"},{"issue":"14","key":"2025120616325442100_hem2025000710C42","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1182\/blood-2018-10-881961","article-title":"A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403","volume":"133","author":"Stock","year":"2019","journal-title":"Blood"},{"issue":"24","key":"2025120616325442100_hem2025000710C43","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1200\/JCO.2017.76.8192","article-title":"Intensified therapy of acute lymphoblastic leukemia in adults: report of the randomized GRAALL-2005 clinical trial","volume":"36","author":"Huguet","year":"2018","journal-title":"J Clin Oncol"},{"issue":"3","key":"2025120616325442100_hem2025000710C44","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/bjh.13847","article-title":"Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003","volume":"172","author":"Hough","year":"2016","journal-title":"Br J Haematol"},{"issue":"3","key":"2025120616325442100_hem2025000710C45","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/leu.2017.265","article-title":"Results of NOPHO ALL2008 treatment for patients aged 1-45 years- with acute lymphoblastic leukemia","volume":"32","author":"Toft","year":"2018","journal-title":"Leukemia"},{"key":"2025120616325442100_hem2025000710C46","first-page":"S118","article-title":"Long-term follow-up of an intensive pediatric regimen for adolescents\/young adults (AYA) with acute lymphoblastic leukemia (ALL): 10-year survival following CALGB 10403 (ALLIANCE)","volume":"9","author":"Stock","year":"2025","journal-title":"HemaSphere, 2025"},{"issue":"1","key":"2025120616325442100_hem2025000710C47","first-page":"27","article-title":"Highlights in acute lymphoblastic leukaemia: European Hematology Association (EHA) 2025","volume":"13","author":"Squibb","year":"2025","journal-title":"Hematology"},{"key":"2025120616325442100_hem2025000710C48","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1182\/blood-2024-209438","article-title":"Addition of inotuzumab to a pediatric inspired chemotherapy regimen in young adult patients with B-cell acute lymphoblastic leukemia: findings from the alliance A041501 phase 3 randomized trial","volume":"144","author":"DeAngelo","year":"2024","journal-title":"Blood"},{"issue":"16_suppl","key":"2025120616325442100_hem2025000710C49","doi-asserted-by":"crossref","first-page":"10016","DOI":"10.1200\/JCO.2023.41.16_suppl.10016","article-title":"A phase 3 trial of inotuzumab ozogamicin for high-risk B-ALL: second safety phase results from Children's Oncology Group AALL1732","volume":"41","author":"O'Brien","year":"2023","journal-title":"J Clin Oncol"},{"issue":"suppl 1","key":"2025120616325442100_hem2025000710C50","first-page":"4211","article-title":"Addition of blinatumomab to consolidation therapy for younger adults BCR:ABL1-negative B-acute lymphoblastic leukemia (ALL) on the ECOG-ACRIN E1910 Phase III trial","volume":"144","author":"Dinner","year":"2024","journal-title":"Blood"},{"issue":"12","key":"2025120616325442100_hem2025000710C51","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1182\/blood-2017-09-806521","article-title":"Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL","volume":"131","author":"Wood","year":"2018","journal-title":"Blood"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2025\/1\/236\/2470377\/236oadwyer.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2025\/1\/236\/2470377\/236oadwyer.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T21:33:04Z","timestamp":1765056784000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2025\/1\/236\/556849\/Immune-targeting-in-Ph-negative-and-Ph-positive-B"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12,5]]},"published-print":{"date-parts":[[2025,12,5]]}},"URL":"https:\/\/doi.org\/10.1182\/hematology.2025000710","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"type":"print","value":"1520-4391"},{"type":"electronic","value":"1520-4383"}],"subject":[],"published-other":{"date-parts":[[2025,12,5]]},"published":{"date-parts":[[2025,12,5]]}}}