Therapeutic Strategies for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies.

Abstract

The treatment landscape for relapsed or refractory acute lymphoblastic leukemia (RR ALL) has evolved significantly with the introduction of monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin. 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-cell 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-disease-burden settings due to its cytoreductive capabilities, blinatumomab shows superior performance in low-disease-burden settings by leveraging preserved T-cell 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-occlusive disease (VOD). Despite these advances, the prognosis for patients with high-risk 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.