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These agents have demonstrated remarkable efficacy, achieving high response rates and minimal residual disease (MRD) negativity. However, the optimal selection, sequencing, and integration of monoclonal antibodies and other modalities like standard chemotherapy or chimeric antigen receptor T\u2010cell therapy remain areas of active investigation. The absence of direct comparative studies has led to reliance on indirect analyses, which provide conflicting results regarding the relative benefits of inotuzumab and blinatumomab. While inotuzumab is preferred in high\u2010disease\u2010burden settings due to its cytoreductive capabilities, blinatumomab shows superior performance in low\u2010disease\u2010burden settings by leveraging preserved T\u2010cell function. Sequential and combination approaches, such as induction with inotuzumab followed by blinatumomab consolidation, may optimize outcomes, particularly for patients undergoing subsequent allogeneic stem cell transplantation (alloSCT). The interval between inotuzumab and alloSCT is critical to mitigate the risk of veno\u2010occlusive disease (VOD). Despite these advances, the prognosis for patients with high\u2010risk genetic lesions, such as TP53 mutations, remains poor, underscoring the need for innovative therapeutic strategies. As monoclonal antibodies increasingly move into frontline therapy, their role in relapse settings must be redefined. Future research should focus on unraveling the molecular underpinnings of resistance and refining treatment paradigms to improve survival and quality of life for patients with RR ALL.<\/jats:p>","DOI":"10.1111\/ejh.14405","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:25:49Z","timestamp":1741728349000},"page":"938-952","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic Strategies for Relapsed or Refractory <scp>B\u2010Cell<\/scp> Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-2404","authenticated-orcid":false,"given":"Antonella","family":"Bruzzese","sequence":"first","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza 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