A review of treatment strategies for elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia

• Novel therapies (BiTEs, ADCs, BCL-2i, CAR T) improve elderly pH⁻ B-ALL survival. • Low-intensity chemotherapy combined with targeted agents enhances efficacy and safety. • Chemotherapy-free regimens achieve deep MRD-negative responses in elderly patients. The treatment of elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (pH⁻ B-ALL) remains challenging because of the high frequency of adverse genetic features, common comorbidities, and significant treatment-related toxicities, which collectively limit the efficacy of conventional chemotherapy and result in poor long-term survival. Recent years have witnessed the emergence of novel targeted agents and immunotherapies, substantially improving the therapeutic outlook for this population. This review summarizes recent advances in the application of low-intensity chemotherapy, CD19/CD22-targeting antibodies such as blinatumomab and inotuzumab ozogamicin, the BCL-2 inhibitor venetoclax, and chimeric antigen receptor (CAR) T-cell therapy for elderly pH⁻ B-ALL patients. Clinical studies indicate that these strategies can increase remission rates and survival while reducing treatment-related toxicity, offering particular benefit to older patients who are unsuitable for intensive chemotherapy. Future efforts should focus on optimizing combination and sequential regimens, as well as personalizing treatment approaches to further improve efficacy and safety.