JAMA Oncol | Recent Advances in Adult Acute Lymphoblastic Leukemia Treatment

This article reviews the 2025 advancements in adult acute lymphoblastic leukemia (ALL) treatment, emphasizing the integrated application of targeted therapy and immunotherapy, which has significantly enhanced patient survival rates and offers important clinical translational value.

 

Literature Overview
This article, 'Management of Adult Acute Lymphoblastic Leukemia in 2025', published in the JAMA Oncology journal, reviews and summarizes the latest treatment strategies for adult ALL. In recent years, treatment approaches have shifted from traditional intensive, long-term chemotherapy to shorter-duration, low-toxicity combination therapies, particularly with the introduction of CD3-CD19 bispecific T-cell engager (BiTE) antibody blinatumomab, CD22 antibody-drug conjugate inotuzumab ozogamicin, and CAR T-cell therapy. These innovations have increased the 4-year overall survival (OS) rate to 85–90% in Ph+ ALL and 80–85% in B-cell ALL.

Background Knowledge
Acute lymphoblastic leukemia (ALL) is a malignant proliferation of B- or T-cell precursors. Adult ALL treatment has long relied on intensive chemotherapy, which carries significant toxicity and poor compliance, particularly in low-resource settings. Recent advances in understanding molecular abnormalities (e.g., BCR::ABL1, KMT2A, Ph-like) have led to the integration of targeted therapies (TKIs) and immunotherapies (e.g., CAR T, BiTE antibodies), substantially improving outcomes. However, elderly patients face challenges due to poor tolerance and high disease heterogeneity. This article systematically summarizes subtype-specific treatment strategies and highlights the critical role of measurable residual disease (MRD) monitoring in prognosis, providing a theoretical foundation and clinical guidance for future precision medicine.

 

 

Research Methods and Experiments
This study reviews multiple clinical trials, including Hyper-CVAD combined with TKI, blinatumomab, or inotuzumab regimens, as well as CAR T-cell therapy for MRD-positive or relapsed/refractory ALL. It further analyzes treatment strategy differences across age groups (<60 vs. ≥60 years) and evaluates the impact of MRD monitoring on disease recurrence and survival rates.

Key Conclusions and Perspectives

• Ph+ ALL treatment has transitioned from traditional chemotherapy-based approaches (Hyper-CVAD+TKI+HSCT) to non-chemotherapy regimens (blinatumomab+TKI), achieving over 85% 4-year OS with reduced toxicity.
• In B-cell ALL, incorporating blinatumomab and inotuzumab significantly improves MRD negativity rates and long-term survival, with 3-year OS reaching 80–90%.
• The mini-Hyper-CVD+inotuzumab+blinatumomab regimen for elderly ALL patients increases 3-year OS from <20% to 46%, while maintaining sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) incidence below 5%.
• MRD monitoring has become essential for evaluating treatment efficacy and guiding subsequent therapy. Next-generation sequencing (NGS) offers 10−6 sensitivity, surpassing traditional flow cytometry (10−4).
• For high-risk ALL (e.g., KMT2A rearrangement, complex karyotype, TP53 mutations), hematopoietic stem cell transplantation (HSCT) remains the preferred consolidation therapy, particularly when NGS-MRD negativity is not achieved.

Research Significance and Prospects
Future research will focus on multi-target antibodies (CD19/20/22), novel CAR T-cell therapies, and shorter-duration, lower-toxicity treatment regimens. Key areas requiring further investigation include optimal TKI duration, discontinuation potential, and efficacy of non-chemotherapy approaches in relapsed/refractory ALL. These advancements provide new directions for personalized treatment and clinical management in ALL.

 

 

Conclusion
This article systematically summarizes the 2025 advancements in adult ALL treatment, particularly highlighting how targeted and immune-based therapies have significantly improved survival and quality of life. With enhanced MRD monitoring and optimized regimens, ALL treatment is evolving toward greater precision and personalization. Subtype-specific strategies (e.g., Ph+, B-cell, T-cell, high-risk genetic) and age-stratified approaches are critical for maximizing efficacy and minimizing toxicity. Future developments in novel antibodies, CAR T-cell therapies, and optimized treatment durations will further reduce reliance on conventional chemotherapy, offering safer and more effective clinical options.

 

Hagop Kantarjian, Ibrahim Aldoss, and Elias Jabbour. Management of Adult Acute Lymphoblastic Leukemia in 2025. JAMA oncology.