Blincyto (blinatumomab)

Bispecific antibodies such as blinatumomab (anti-CD19), antibody-drug conjugates like inotuzumab ozogamicin (anti-CD22), and monoclonal antibodies such as daratumumab (anti-CD38) have demonstrated efficacy in relapsed or refractory disease with improved safety profiles. The integration of targeted and immune-based therapies into conventional regimens represents a decisive step toward precision medicine, aiming to enhance survival outcomes while reducing treatment-related toxicity and improving quality of life in ALL children. This review aims to provide a comprehensive overview of the current understanding of ALL pathobiology and therapeutic approaches, with particular emphasis on the expanding role of immunotherapeutic strategies in pediatric disease.

Post-HCT azacitidine may have a role for MRD-positive AML. In AML with FLT3-internal tandem duplication mutation, post-HCT gilteritinib and sorafenib can be evidence-based strategies to target MRD. In ALL, blinatumomab is a powerful tool to eradicate MRD in patients with Philadelphia (Ph)-positive or Ph-negative ALL; tyrosine kinase inhibitors are indicated for post-HCT management of Ph+ ALL. Despite these advances, the optimal duration and type of intervention still remain unknown for many patients with acute leukemia who have peri-HCT MRD.

Blinatumomab and inotuzumab ozogamicin have become established treatments, enhancing remission rates, measurable residual disease clearance, and overall survival in relapsed/refractory disease, and these agents, are now increasingly incorporated into frontline therapy...In acute myeloid leukemia (AML), gemtuzumab ozogamicin has shown significant clinical benefits, particularly in molecularly defined subsets...This review highlights how immunotherapy has reshaped treatment paradigms across acute leukemias, underscoring successful experiences in B-ALL. These insights emphasize the need for continued innovation to overcome existing hurdles in AML and T-ALL, ultimately aiming to enhance patient outcomes and quality of life.

CD24 therefore emerged as an effective target in BCP-ALL, and the combination of CD24 and CD123 as a potential effective double-targeting strategy. The combination of different recognition modalities (eg, a CAR and CD16) should be tested to determine whether it provides synergistic cytotoxic activity in triple targeting.

Patients ≥60 years with Ph-negative B-cell ALL and TP53 VAF ≥45% had poor outcomes, with 4-year event-free survival (EFS) and overall survival (OS) of 28%, driven primarily by increased relapse risk, even among patients treated with frontline inotuzumab ozogamicin (INO) and/or blinatumomab. TP53 persistence at remission occurred in 44% of tested patients and was associated with increased ALL relapse risk. These results demonstrate that TP53 VAF is prognostic in older patients with Ph-negative B-cell ALL; high VAF may increase relapse risk but is not independently associated with survival in younger patients.

It highlights an unusual and serious pattern of relapse in an extramedullary site following blinatumomab therapy. Clinicians should remain vigilant for signs of lineage switch and extramedullary disease during treatment, particularly in patients with KMT2A-rearranged B-ALL, and consider imaging or biopsy when new neurologic or systemic symptoms arise.

Variations in OS appear driven by patient heterogeneity and concurrent chemotherapy intensity rather than blinatumomab timing. Future studies should refine its integration within targeted and genomically defined strategies, particularly for high-risk subsets such as Ph-like and KMT2A-rearranged B-ALL.

While the patient failed high-risk T-LBLL induction therapy, blinatumomab followed by decitabine and venetoclax induced a morphologic remission. This case illustrated the importance of integrating MFC analysis with NGS data to provide individualized patient treatment. The authors have confirmed clinical trial registration is not needed for this submission.

P1, N=35, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Nov 2025 | Trial primary completion date: Jun 2026 --> Nov 2025

Recent advances in immunotherapy, including blinatumomab, inotuzumab ozogamicin, and CD19-directed CAR T-cell therapy, have shown significant efficacy and favorable tolerability in pediatric and adult DS-ALL. Emerging approaches incorporating early immunotherapy, MRD-guided treatment, and chemotherapy-free regimens may improve survival and quality of life. Prospective DS-specific trials are essential to optimize therapy and close the outcome gap in this high-risk population.

Ponatinib has been successfully integrated into various treatment regimens, including both low- and high-intensity chemotherapy regimens, and in combination with blinatumomab, for adult patients with newly diagnosed Ph+ ALL. Herein, we summarize landmark trials, specifically their efficacy and toxicity profile, that established ponatinib as a standard of care for patients with newly diagnosed Ph+ ALL who are suitable medically for it.

P2, N=18, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting